General Information:

Id: 2,814
Diseases: Cancer
Diabetes mellitus, type II - [OMIM]
Insulin resistance
Metabolic syndrome
Mammalia
review
Reference: Braun S et al.(2011) The link between the metabolic syndrome and cancer Int. J. Biol. Sci. 7: 1003-1015 [PMID: 21912508]

Interaction Information:

Comment Low HDL-C serum levels were associated with lung cancer incidence as well as the Non-Hodgkin lymphoma (NHL) and was suggested to be a marker for increased breast cancer risk in pre-menopausal as well as post-menopausal women, since it might reflect an unfavorable hormonal profile with particularly increased estrogen levels especially in obese women.
Formal Description
Interaction-ID: 25932

increases_activity of

disease

Non-Hodgkin lymphoma

Comment Low HDL-C serum levels were associated with lung cancer incidence as well as the Non-Hodgkin lymphoma (NHL) and was suggested to be a marker for increased breast cancer risk in pre-menopausal as well as post-menopausal women, since it might reflect an unfavorable hormonal profile with particularly increased estrogen levels especially in obese women.
Formal Description
Interaction-ID: 25933

increases_activity of

disease

Lung cancer

Comment Low HDL-C serum levels were associated with lung cancer incidence as well as the Non-Hodgkin lymphoma (NHL) and was suggested to be a marker for increased breast cancer risk in pre-menopausal as well as post-menopausal women, since it might reflect an unfavorable hormonal profile with particularly increased estrogen levels especially in obese women.
Formal Description
Interaction-ID: 25934

increases_activity of

disease

Breast cancer

Comment High serum levels of total cholesterol and TG raise the risk of prostate and post-menopausal breast cancer.
Formal Description
Interaction-ID: 25935

phenotype

increased circulating cholesterol and triglyceride level

increases_activity of

disease

Prostate cancer

Comment High serum levels of total cholesterol and TG raise the risk of prostate and post-menopausal breast cancer.
Formal Description
Interaction-ID: 25937

phenotype

increased circulating cholesterol and triglyceride level

increases_activity of

disease

Breast cancer

in postmenopausal women
Comment Low LDL-C serum levels were also linked to an 15-fold increased risk of developing hematological cancer.
Formal Description
Interaction-ID: 25938

increases_activity of

disease

Hematological cancer

Comment Independent of a high body mass, T2DM acts as a predictor of mortality from cancer of the colon, pancreas, female breast, male liver and bladder.
Formal Description
Interaction-ID: 25939

increases_activity of

Comment Independent of a high body mass, T2DM acts as a predictor of mortality from cancer of the colon, pancreas, female breast, male liver and bladder.
Formal Description
Interaction-ID: 25940

increases_activity of

Comment Independent of a high body mass, T2DM acts as a predictor of mortality from cancer of the colon, pancreas, female breast, male liver and bladder.
Formal Description
Interaction-ID: 25941

increases_activity of

disease

Breast cancer

in women
Comment Independent of a high body mass, T2DM acts as a predictor of mortality from cancer of the colon, pancreas, female breast, male liver and bladder.
Formal Description
Interaction-ID: 25942

increases_activity of

in men
Comment Independent of a high body mass, T2DM acts as a predictor of mortality from cancer of the colon, pancreas, female breast, male liver and bladder.
Formal Description
Interaction-ID: 25943

increases_activity of

disease

Bladder cancer

in men
Comment IGF-1R and IR have been found to be overexpressed in cancer cells.
Formal Description
Interaction-ID: 25944

disease

Cancer

increases_expression of

gene/protein

IGF1R

Drugbank entries Show/Hide entries for IGF1R
Comment IGF-1R and IR have been found to be overexpressed in cancer cells.
Formal Description
Interaction-ID: 25945

disease

Cancer

increases_expression of

gene/protein

INSR

Drugbank entries Show/Hide entries for INSR
Comment The PI3K signaling cascade is a major pathway of the IGF-1R and IR and commenly deregulated in cancer cells.
Formal Description
Interaction-ID: 25946

complex/PPI

Insulin-like growth factor 1 receptor

increases_activity of

Comment The PI3K signaling cascade is a major pathway of the IGF-1R and IR and commenly deregulated in cancer cells.
Formal Description
Interaction-ID: 25951

complex/PPI

Insulin receptor

increases_activity of

Comment Hyperinsulinemia was shown to increase the IGF-1 production of the liver.
Formal Description
Interaction-ID: 25952

increases_quantity of

gene/protein

IGF1

in liver
Drugbank entries Show/Hide entries for IGF1
Comment Breast cancer does not generally produce IGF-1 but does express and secrete small amounts of IGF-2.
Formal Description
Interaction-ID: 25953

disease

Breast cancer

increases_quantity of

gene/protein

IGF2

Comment Estrogen was found to induce IGF-1 receptor expression in estrogen receptor-positive breast cancer cell lines.
Formal Description
Interaction-ID: 25954

drug/chemical compound

Estrogen

increases_expression of

gene/protein

IGF1R

in estrogen receptor-positive breast cancer cell lines
Drugbank entries Show/Hide entries for IGF1R
Comment Both the IR and the IGF-1R are transmembrane oligomer receptors which consist of one alpha- and one beta-subunit. The beta-subunit comprises a tyrosine kinase which undergoes autophosphorylation after the ligand binds to the extracellular alpha-subunit of the receptor.
Formal Description
Interaction-ID: 25956

is_part_of

complex/PPI

Insulin-like growth factor 1 receptor

Comment Both the IR and the IGF-1R are transmembrane oligomer receptors which consist of one alpha- and one beta-subunit. The beta-subunit comprises a tyrosine kinase which undergoes autophosphorylation after the ligand binds to the extracellular alpha-subunit of the receptor.
Formal Description
Interaction-ID: 25957

is_part_of

complex/PPI

Insulin-like growth factor 1 receptor

Comment Both the IR and the IGF-1R are transmembrane oligomer receptors which consist of one alpha- and one beta-subunit. The beta-subunit comprises a tyrosine kinase which undergoes autophosphorylation after the ligand binds to the extracellular alpha-subunit of the receptor.
Formal Description
Interaction-ID: 25960

is_part_of

complex/PPI

Insulin receptor

Comment Both the IR and the IGF-1R are transmembrane oligomer receptors which consist of one alpha- and one beta-subunit. The beta-subunit comprises a tyrosine kinase which undergoes autophosphorylation after the ligand binds to the extracellular alpha-subunit of the receptor.
Formal Description
Interaction-ID: 25961

is_part_of

complex/PPI

Insulin receptor

Comment Cells that express the IR and the IGF-1R may also form a hybrid receptor from two subunits of these two receptors. Insulin manifests a decreased affinity to the IGF-1R and a very low affinity to the hybrid receptors. However IGF-1 retains its high affinity to the IGF-1R as well as to the hybrid receptors.
Formal Description
Interaction-ID: 25998

is_part_of

complex/PPI

INSR-IGF1R hybrid complex

Comment Cells that express the IR and the IGF-1R may also form a hybrid receptor from two subunits of these two receptors. Insulin manifests a decreased affinity to the IGF-1R and a very low affinity to the hybrid receptors. However IGF-1 retains its high affinity to the IGF-1R as well as to the hybrid receptors.
Formal Description
Interaction-ID: 25999

is_part_of

complex/PPI

INSR-IGF1R hybrid complex

Comment Cells that express the IR and the IGF-1R may also form a hybrid receptor from two subunits of these two receptors. Insulin manifests a decreased affinity to the IGF-1R and a very low affinity to the hybrid receptors. However IGF-1 retains its high affinity to the IGF-1R as well as to the hybrid receptors.
Formal Description
Interaction-ID: 26000

is_part_of

complex/PPI

INSR-IGF1R hybrid complex

Comment Cells that express the IR and the IGF-1R may also form a hybrid receptor from two subunits of these two receptors. Insulin manifests a decreased affinity to the IGF-1R and a very low affinity to the hybrid receptors. However IGF-1 retains its high affinity to the IGF-1R as well as to the hybrid receptors.
Formal Description
Interaction-ID: 26001

is_part_of

complex/PPI

INSR-IGF1R hybrid complex

Comment The insulin receptor (IR) has two subtypes IR-A and IR-B, which result from alternative splicing of the INSR gene. As the IR-A homoreceptor, the IGF-1R/IR-A hybrid receptor mainly results in mitogenic signalling. Comparatively the IGF-1R/IR-B hybrid receptor results in metabolic signaling.
Formal Description
Interaction-ID: 26002

complex/PPI

Insulin receptor subtype A

affects_activity of

Comment The insulin receptor (IR) has two subtypes IR-A and IR-B, which result from alternative splicing of the INSR gene. As the IR-A homoreceptor, the IGF-1R/IR-A hybrid receptor mainly results in mitogenic signalling. Comparatively the IGF-1R/IR-B hybrid receptor results in metabolic signaling.
Formal Description
Interaction-ID: 26003

complex/PPI

INSR-B - IGF1R hybrid complex

affects_activity of

process

regulation of metabolic signaling

Comment PI3K signaling activates Akt resulting in activation of mTOR and thus, mediating its effects on cell growth by increasing ribosomal protein synthesis and preparation of mitosis through S6k1 and 4E-BP-1. Activation of mTOR results in protein synthesis, cell growth and the preparation of cells for mitosis, all mechanisms that favor tumor growth. Dysregulated signaling of mTOR has been linked to numerous human cancers.
Formal Description
Interaction-ID: 26004

increases_activity of

gene/protein

AKT1

Drugbank entries Show/Hide entries for AKT1
Comment PI3K signaling activates Akt resulting in activation of mTOR and thus, mediating its effects on cell growth by increasing ribosomal protein synthesis and preparation of mitosis through S6k1 and 4E-BP-1. Activation of mTOR results in protein synthesis, cell growth and the preparation of cells for mitosis, all mechanisms that favor tumor growth. Dysregulated signaling of mTOR has been linked to numerous human cancers.
Formal Description
Interaction-ID: 26005

gene/protein

AKT1

increases_activity of

gene/protein

MTOR

Drugbank entries Show/Hide entries for AKT1 or MTOR
Comment Binding of IGF-1 or IGF-2 or insulin to the IGF-1R alpha-subunit leads to autophosphorylation of beta-subunit residues, which then act as docking site to insulin receptor substrates (IRS-1 to 4).
Formal Description
Interaction-ID: 26006

gene/protein

IGF1

increases_activity of

complex/PPI

Insulin-like growth factor 1 receptor

Drugbank entries Show/Hide entries for IGF1
Comment Binding of IGF-1 or IGF-2 or insulin to the IGF-1R alpha-subunit leads to autophosphorylation of beta-subunit residues, which then act as docking site to insulin receptor substrates (IRS-1 to 4).
Formal Description
Interaction-ID: 26007

gene/protein

IGF2

increases_activity of

complex/PPI

Insulin-like growth factor 1 receptor

Comment Binding of IGF-1 or IGF-2 or insulin to the IGF-1R alpha-subunit leads to autophosphorylation of beta-subunit residues, which then act as docking site to insulin receptor substrates (IRS-1 to 4).
Formal Description
Interaction-ID: 26008

complex/PPI

Insulin

increases_activity of

complex/PPI

Insulin-like growth factor 1 receptor

Comment Binding of IGF-1 or IGF-2 or insulin to the IGF-1R alpha-subunit leads to autophosphorylation of beta-subunit residues, which then act as docking site to insulin receptor substrates (IRS-1 to 4).
Formal Description
Interaction-ID: 26009

complex/PPI

Insulin-like growth factor 1 receptor

increases_activity of

gene/protein

IRS1

Drugbank entries Show/Hide entries for IRS1
Comment Binding of IGF-1 or IGF-2 or insulin to the IGF-1R alpha-subunit leads to autophosphorylation of beta-subunit residues, which then act as docking site to insulin receptor substrates (IRS-1 to 4).
Formal Description
Interaction-ID: 26010

complex/PPI

Insulin-like growth factor 1 receptor

increases_activity of

gene/protein

IRS2

Comment Binding of IGF-1 or IGF-2 or insulin to the IGF-1R alpha-subunit leads to autophosphorylation of beta-subunit residues, which then act as docking site to insulin receptor substrates (IRS-1 to 4).
Formal Description
Interaction-ID: 26011

complex/PPI

Insulin-like growth factor 1 receptor

increases_activity of

gene/protein

IRS3

Comment Binding of IGF-1 or IGF-2 or insulin to the IGF-1R alpha-subunit leads to autophosphorylation of beta-subunit residues, which then act as docking site to insulin receptor substrates (IRS-1 to 4).
Formal Description
Interaction-ID: 26012

complex/PPI

Insulin-like growth factor 1 receptor

increases_activity of

gene/protein

IRS4

Comment Bound IRS-1 results in PI3K activation, which in turn activates Akt.
Formal Description
Interaction-ID: 26013

gene/protein

IRS1

increases_activity of

complex/PPI

Phosphatidylinositol 3-kinase

Drugbank entries Show/Hide entries for IRS1
Comment Bound IRS-1 results in PI3K activation, which in turn activates Akt.
Formal Description
Interaction-ID: 26014

complex/PPI

Phosphatidylinositol 3-kinase

increases_activity of

gene/protein

AKT1

Drugbank entries Show/Hide entries for AKT1
Comment The tumor suppressor phosphates and tensin homolog deleted on chromosome 10 (PTEN) inhibits PI3K by dephosphorylation.
Formal Description
Interaction-ID: 26015

gene/protein

PTEN

decreases_activity of

complex/PPI

Phosphatidylinositol 3-kinase

Comment Activated Akt has many substrates; in one pathway Akt inhibits apoptosis by inactivating BCL-2 antagonist of cell death (BAD), and in the second pathway Akt regulates protein synthesis by phosphorylating tuberous sclerosis complex (TSC1/2). This phosphorylation removes the inhibition of TSC from mammalian target of rapamycin (mTOR).
Formal Description
Interaction-ID: 26016

gene/protein

AKT1

decreases_activity of

gene/protein

BAD

Drugbank entries Show/Hide entries for AKT1
Comment Activated Akt has many substrates; in one pathway Akt inhibits apoptosis by inactivating BCL-2 antagonist of cell death (BAD), and in the second pathway Akt regulates protein synthesis by phosphorylating tuberous sclerosis complex (TSC1/2). This phosphorylation removes the inhibition of TSC from mammalian target of rapamycin (mTOR).
Formal Description
Interaction-ID: 26017

gene/protein

AKT1

decreases_activity of

Drugbank entries Show/Hide entries for AKT1
Comment Activated Akt has many substrates; in one pathway Akt inhibits apoptosis by inactivating BCL-2 antagonist of cell death (BAD), and in the second pathway Akt regulates protein synthesis by phosphorylating tuberous sclerosis complex (TSC1/2). This phosphorylation removes the inhibition of TSC from mammalian target of rapamycin (mTOR).
Formal Description
Interaction-ID: 26018

gene/protein

AKT1

affects_activity of

Drugbank entries Show/Hide entries for AKT1
Comment Activated Akt has many substrates; in one pathway Akt inhibits apoptosis by inactivating BCL-2 antagonist of cell death (BAD), and in the second pathway Akt regulates protein synthesis by phosphorylating tuberous sclerosis complex (TSC1/2). This phosphorylation removes the inhibition of TSC from mammalian target of rapamycin (mTOR).
Formal Description
Interaction-ID: 26019

gene/protein

AKT1

decreases_activity of

complex/PPI

TSC1-TSC2 complex

Drugbank entries Show/Hide entries for AKT1
Comment Activated Akt has many substrates; in one pathway Akt inhibits apoptosis by inactivating BCL-2 antagonist of cell death (BAD), and in the second pathway Akt regulates protein synthesis by phosphorylating tuberous sclerosis complex (TSC1/2). This phosphorylation removes the inhibition of TSC from mammalian target of rapamycin (mTOR).
Formal Description
Interaction-ID: 26020

complex/PPI

TSC1-TSC2 complex

decreases_activity of

gene/protein

MTOR

Drugbank entries Show/Hide entries for MTOR
Comment mTOR activates the ribosomal S6 kinase (S6K) and eukaryotic initiation factor 4E-binding protein-1 (4E-BP-1), leading to protein synthesis.
Formal Description
Interaction-ID: 26021

gene/protein

MTOR

increases_activity of

gene/protein

RPS6KB1

Drugbank entries Show/Hide entries for MTOR
Comment mTOR activates the ribosomal S6 kinase (S6K) and eukaryotic initiation factor 4E-binding protein-1 (4E-BP-1), leading to protein synthesis.
Formal Description
Interaction-ID: 26022

gene/protein

MTOR

increases_activity of

gene/protein

EIF4EBP1

Drugbank entries Show/Hide entries for MTOR
Comment mTOR activates the ribosomal S6 kinase (S6K) and eukaryotic initiation factor 4E-binding protein-1 (4E-BP-1), leading to protein synthesis.
Formal Description
Interaction-ID: 26023

gene/protein

MTOR

increases_activity of

process

translation

Drugbank entries Show/Hide entries for MTOR
Comment In energy depletion expression of the suppressor gene LKB1 and AMP raise. AMPK is activated by both mechanisms. AMPK inhibits protein synthesis through direct inhibition of mTOR or indirectly by activating the TSC complex.
Formal Description
Interaction-ID: 26024

process

response to energy depletion

increases_expression of

gene/protein

STK11

Comment In energy depletion expression of the suppressor gene LKB1 and AMP raise. AMPK is activated by both mechanisms. AMPK inhibits protein synthesis through direct inhibition of mTOR or indirectly by activating the TSC complex.
Formal Description
Interaction-ID: 26025

process

response to energy depletion

increases_quantity of

drug/chemical compound

AMP

Comment In energy depletion expression of the suppressor gene LKB1 and AMP raise. AMPK is activated by both mechanisms. AMPK inhibits protein synthesis through direct inhibition of mTOR or indirectly by activating the TSC complex.
Formal Description
Interaction-ID: 26026

gene/protein

STK11

increases_activity of

complex/PPI

AMPK

Comment In energy depletion expression of the suppressor gene LKB1 and AMP raise. AMPK is activated by both mechanisms. AMPK inhibits protein synthesis through direct inhibition of mTOR or indirectly by activating the TSC complex.
Formal Description
Interaction-ID: 26027

drug/chemical compound

AMP

increases_activity of

complex/PPI

AMPK

Comment In energy depletion expression of the suppressor gene LKB1 and AMP raise. AMPK is activated by both mechanisms. AMPK inhibits protein synthesis through direct inhibition of mTOR or indirectly by activating the TSC complex.
Formal Description
Interaction-ID: 26028

complex/PPI

AMPK

decreases_activity of

gene/protein

MTOR

Drugbank entries Show/Hide entries for MTOR
Comment In energy depletion expression of the suppressor gene LKB1 and AMP raise. AMPK is activated by both mechanisms. AMPK inhibits protein synthesis through direct inhibition of mTOR or indirectly by activating the TSC complex.
Formal Description
Interaction-ID: 26029

complex/PPI

AMPK

increases_activity of

complex/PPI

TSC1-TSC2 complex

Comment The mitogen-activated protein kinase (MAPK) pathway can also be activated by IGF-1R activation. In this pathway IGF-1R activates the adaptor proteins, Shc and Grb2, leading to activation of Ras, Raf, MEK1/2, and ERK1/2, which results in cell proliferation.
Formal Description
Interaction-ID: 26030

complex/PPI

Insulin-like growth factor 1 receptor

increases_activity of

Comment The mitogen-activated protein kinase (MAPK) pathway can also be activated by IGF-1R activation. In this pathway IGF-1R activates the adaptor proteins, Shc and Grb2, leading to activation of Ras, Raf, MEK1/2, and ERK1/2, which results in cell proliferation.
Formal Description
Interaction-ID: 26031

complex/PPI

Insulin-like growth factor 1 receptor

increases_activity of

complex/PPI

SHC-GRB2 complex

Comment The mitogen-activated protein kinase (MAPK) pathway can also be activated by IGF-1R activation. In this pathway IGF-1R activates the adaptor proteins, Shc and Grb2, leading to activation of Ras, Raf, MEK1/2, and ERK1/2, which results in cell proliferation.
Formal Description
Interaction-ID: 26032

complex/PPI

SHC-GRB2 complex

increases_activity of

gene/protein

RAS

Comment The mitogen-activated protein kinase (MAPK) pathway can also be activated by IGF-1R activation. In this pathway IGF-1R activates the adaptor proteins, Shc and Grb2, leading to activation of Ras, Raf, MEK1/2, and ERK1/2, which results in cell proliferation.
Formal Description
Interaction-ID: 26033

gene/protein

RAS

increases_activity of

gene/protein

RAF

Comment The mitogen-activated protein kinase (MAPK) pathway can also be activated by IGF-1R activation. In this pathway IGF-1R activates the adaptor proteins, Shc and Grb2, leading to activation of Ras, Raf, MEK1/2, and ERK1/2, which results in cell proliferation.
Formal Description
Interaction-ID: 26034

gene/protein

RAF

increases_activity of

gene/protein

MAP2K1/2

Comment The mitogen-activated protein kinase (MAPK) pathway can also be activated by IGF-1R activation. In this pathway IGF-1R activates the adaptor proteins, Shc and Grb2, leading to activation of Ras, Raf, MEK1/2, and ERK1/2, which results in cell proliferation.
Formal Description
Interaction-ID: 26035

gene/protein

MAP2K1/2

increases_activity of

gene/protein

MAPK3/1

Comment The mitogen-activated protein kinase (MAPK) pathway can also be activated by IGF-1R activation. In this pathway IGF-1R activates the adaptor proteins, Shc and Grb2, leading to activation of Ras, Raf, MEK1/2, and ERK1/2, which results in cell proliferation.
Formal Description
Interaction-ID: 26036

gene/protein

MAPK3/1

increases_activity of

Comment Activation of mTOR results in protein synthesis, cell growth and the preparation of cells for mitosis, all mechanisms that favor tumor growth. Dysregulated signaling of mTOR has been linked to numerous human cancers.
Formal Description
Interaction-ID: 26037

gene/protein

MTOR

affects_activity of

disease

Cancer

Drugbank entries Show/Hide entries for MTOR
Comment mTOR was found to be inhibited by hypoxia.
Formal Description
Interaction-ID: 26038

decreases_activity of

gene/protein

MTOR

Drugbank entries Show/Hide entries for MTOR
Comment PTEN is, after p53, the most commonly mutated tumor suppressor gene in human cancer. A mutation or inactivation of at least one copy of PTEN emerges in more than 50% of women breast cancer. In MCF-7 breast cancer cells it has been shown that a loss of PTEN results in an increased signaling of IGF-2 mediating through the IGF-1R and IR-A.
Formal Description
Interaction-ID: 26040

gene/protein

PTEN

affects_activity of

disease

Breast cancer

Comment PTEN is, after p53, the most commonly mutated tumor suppressor gene in human cancer. A mutation or inactivation of at least one copy of PTEN emerges in more than 50% of women breast cancer. In MCF-7 breast cancer cells it has been shown that a loss of PTEN results in an increased signaling of IGF-2 mediating through the IGF-1R and IR-A.
Formal Description
Interaction-ID: 26047

gene/protein

PTEN

affects_activity of

gene/protein

IGF2

Comment Breast and prostate cancer cell lines were found to display an enhanced level of IGF-1R and decreased level of IR.
Formal Description
Interaction-ID: 26048

disease

Breast cancer

increases_quantity of

complex/PPI

Insulin-like growth factor 1 receptor

Comment Breast and prostate cancer cell lines were found to display an enhanced level of IGF-1R and decreased level of IR.
Formal Description
Interaction-ID: 26049

disease

Breast cancer

decreases_quantity of

complex/PPI

Insulin receptor

Comment Breast and prostate cancer cell lines were found to display an enhanced level of IGF-1R and decreased level of IR.
Formal Description
Interaction-ID: 26050

disease

Prostate cancer

increases_quantity of

complex/PPI

Insulin-like growth factor 1 receptor

Comment Breast and prostate cancer cell lines were found to display an enhanced level of IGF-1R and decreased level of IR.
Formal Description
Interaction-ID: 26051

disease

Prostate cancer

decreases_quantity of

complex/PPI

Insulin receptor

Comment A resistance to chemotherapeutic agents like trastuzumab and tamoxifen in breast cancer cell lines was associated with an activation of mTOR. One activator of mTOR and thus promoter of cell growth and proliferation is displayed by AKT. Metformin was found to activate AMPK and decrease AKT and insulin levels in mice. Both mechanisms result in a decreased signaling of cell growth. This might explain why Metformin is associated with a decreased risk of cancer development and a better response to chemotherapy in patients with breast cancer.
Formal Description
Interaction-ID: 26052

gene/protein

MTOR

decreases_activity of

drug/chemical compound

Trastuzumab

Drugbank entries Show/Hide entries for MTOR or Trastuzumab
Comment A resistance to chemotherapeutic agents like trastuzumab and tamoxifen in breast cancer cell lines was associated with an activation of mTOR. One activator of mTOR and thus promoter of cell growth and proliferation is displayed by AKT. Metformin was found to activate AMPK and decrease AKT and insulin levels in mice. Both mechanisms result in a decreased signaling of cell growth. This might explain why Metformin is associated with a decreased risk of cancer development and a better response to chemotherapy in patients with breast cancer.
Formal Description
Interaction-ID: 26053

gene/protein

MTOR

decreases_activity of

drug/chemical compound

Tamoxifen

Drugbank entries Show/Hide entries for MTOR or Tamoxifen
Comment A resistance to chemotherapeutic agents like trastuzumab and tamoxifen in breast cancer cell lines was associated with an activation of mTOR. One activator of mTOR and thus promoter of cell growth and proliferation is displayed by AKT. Metformin was found to activate AMPK and decrease AKT and insulin levels in mice. Both mechanisms result in a decreased signaling of cell growth. This might explain why Metformin is associated with a decreased risk of cancer development and a better response to chemotherapy in patients with breast cancer.
Formal Description
Interaction-ID: 26054

drug/chemical compound

Metformin

increases_activity of

complex/PPI

AMPK

Drugbank entries Show/Hide entries for Metformin
Comment A resistance to chemotherapeutic agents like trastuzumab and tamoxifen in breast cancer cell lines was associated with an activation of mTOR. One activator of mTOR and thus promoter of cell growth and proliferation is displayed by AKT. Metformin was found to activate AMPK and decrease AKT and insulin levels in mice. Both mechanisms result in a decreased signaling of cell growth. This might explain why Metformin is associated with a decreased risk of cancer development and a better response to chemotherapy in patients with breast cancer.
Formal Description
Interaction-ID: 26055

drug/chemical compound

Metformin

decreases_quantity of

gene/protein

AKT1

Drugbank entries Show/Hide entries for Metformin or AKT1
Comment A resistance to chemotherapeutic agents like trastuzumab and tamoxifen in breast cancer cell lines was associated with an activation of mTOR. One activator of mTOR and thus promoter of cell growth and proliferation is displayed by AKT. Metformin was found to activate AMPK and decrease AKT and insulin levels in mice. Both mechanisms result in a decreased signaling of cell growth. This might explain why Metformin is associated with a decreased risk of cancer development and a better response to chemotherapy in patients with breast cancer.
Formal Description
Interaction-ID: 26056

drug/chemical compound

Metformin

decreases_quantity of

complex/PPI

Insulin

Drugbank entries Show/Hide entries for Metformin
Comment Hyperinsulinemia and obesity cause an increased production of hepatic IGF-1 by a enhanced signaling of the GHR in the liver. This in turn, raises the amount of circulating IGF-1 and therefore results in cell growth and proliferation.
Formal Description
Interaction-ID: 26057

increases_quantity of

gene/protein

IGF1

Drugbank entries Show/Hide entries for IGF1
Comment Hyperinsulinemia and obesity cause an increased production of hepatic IGF-1 by a enhanced signaling of the GHR in the liver. This in turn, raises the amount of circulating IGF-1 and therefore results in cell growth and proliferation.
Formal Description
Interaction-ID: 26058

disease

Obesity

increases_quantity of

gene/protein

IGF1

Drugbank entries Show/Hide entries for IGF1
Comment The enhanced percentage of fat tissue in obesity delivers an augmented level of aromatase, which results in an increased synthesis of estrogen. Furthermore, obesity as well as hyperinsulinemia and elevated IGF-1 levels were shown to reduce the production of sex hormone-binding globulin (SHBG). This also leads to an increased bioavailability of estrogen.
Formal Description
Interaction-ID: 26060

disease

Obesity

increases_quantity of

gene/protein

CYP19A1

Drugbank entries Show/Hide entries for CYP19A1
Comment The enhanced percentage of fat tissue in obesity delivers an augmented level of aromatase, which results in an increased synthesis of estrogen. Furthermore, obesity as well as hyperinsulinemia and elevated IGF-1 levels were shown to reduce the production of sex hormone-binding globulin (SHBG). This also leads to an increased bioavailability of estrogen.
Formal Description
Interaction-ID: 26061

gene/protein

CYP19A1

increases_quantity of

drug/chemical compound

Estrogen

Drugbank entries Show/Hide entries for CYP19A1
Comment The enhanced percentage of fat tissue in obesity delivers an augmented level of aromatase, which results in an increased synthesis of estrogen. Furthermore, obesity as well as hyperinsulinemia and elevated IGF-1 levels were shown to reduce the production of sex hormone-binding globulin (SHBG). This also leads to an increased bioavailability of estrogen.
Formal Description
Interaction-ID: 26062

disease

Obesity

decreases_quantity of

gene/protein

SHBG

Comment The enhanced percentage of fat tissue in obesity delivers an augmented level of aromatase, which results in an increased synthesis of estrogen. Furthermore, obesity as well as hyperinsulinemia and elevated IGF-1 levels were shown to reduce the production of sex hormone-binding globulin (SHBG). This also leads to an increased bioavailability of estrogen.
Formal Description
Interaction-ID: 26063

decreases_quantity of

gene/protein

SHBG

Comment The enhanced percentage of fat tissue in obesity delivers an augmented level of aromatase, which results in an increased synthesis of estrogen. Furthermore, obesity as well as hyperinsulinemia and elevated IGF-1 levels were shown to reduce the production of sex hormone-binding globulin (SHBG). This also leads to an increased bioavailability of estrogen.
Formal Description
Interaction-ID: 26064

gene/protein

SHBG

decreases_quantity of

drug/chemical compound

Estrogen

Comment Estrogen was demonstrated to induce the expression of the IGF-1R as well as the insulin recep-tor substrates IRS-1 and IRS-2.
Formal Description
Interaction-ID: 26065

drug/chemical compound

Estrogen

increases_expression of

gene/protein

IGF1R

Drugbank entries Show/Hide entries for IGF1R
Comment Estrogen was demonstrated to induce the expression of the IGF-1R as well as the insulin recep-tor substrates IRS-1 and IRS-2.
Formal Description
Interaction-ID: 26066

drug/chemical compound

Estrogen

increases_expression of

gene/protein

IRS1

Drugbank entries Show/Hide entries for IRS1
Comment Estrogen was demonstrated to induce the expression of the IGF-1R as well as the insulin recep-tor substrates IRS-1 and IRS-2.
Formal Description
Interaction-ID: 26067

drug/chemical compound

Estrogen

increases_expression of

gene/protein

IRS2

Comment Leptin and insulin as well as TNF-alpha and IL-6 are known to induce aromatase and thus stimulate estrogen biosynthesis. These results might explain the connection of the enhanced growth of breast cancer in patients with T2DM and obesity.
Formal Description
Interaction-ID: 26069

gene/protein

TNF

increases_expression of

gene/protein

CYP19A1

Drugbank entries Show/Hide entries for TNF or CYP19A1
Comment Leptin and insulin as well as TNF-alpha and IL-6 are known to induce aromatase and thus stimulate estrogen biosynthesis. These results might explain the connection of the enhanced growth of breast cancer in patients with T2DM and obesity.
Formal Description
Interaction-ID: 26071

gene/protein

IL6

increases_expression of

gene/protein

CYP19A1

Drugbank entries Show/Hide entries for IL6 or CYP19A1
Comment Leptin and insulin as well as TNF-alpha and IL-6 are known to induce aromatase and thus stimulate estrogen biosynthesis. These results might explain the connection of the enhanced growth of breast cancer in patients with T2DM and obesity.
Formal Description
Interaction-ID: 26072

gene/protein

LEP

increases_expression of

gene/protein

CYP19A1

Drugbank entries Show/Hide entries for CYP19A1
Comment Leptin and insulin as well as TNF-alpha and IL-6 are known to induce aromatase and thus stimulate estrogen biosynthesis. These results might explain the connection of the enhanced growth of breast cancer in patients with T2DM and obesity.
Formal Description
Interaction-ID: 26074

complex/PPI

Insulin

increases_expression of

gene/protein

CYP19A1

Drugbank entries Show/Hide entries for CYP19A1
Comment By activation of AMP-activated protein kinase (AMPK) and thus indirectly suppressing mTOR, adiponectin was found to inhibit colorectal cancer cell growth.
Formal Description
Interaction-ID: 26075

gene/protein

ADIPOQ

decreases_activity of

Comment By activation of AMP-activated protein kinase (AMPK) and thus indirectly suppressing mTOR, adiponectin was found to inhibit colorectal cancer cell growth.
Formal Description
Interaction-ID: 26076

gene/protein

ADIPOQ

increases_activity of

complex/PPI

AMPK

Comment Adiponectin is considered to have anticancer effects because of its anti-inflammatory character and further was found to be a negative regulator of angiogenesis.
Formal Description
Interaction-ID: 26078

gene/protein

ADIPOQ

decreases_activity of

Comment Adiponectin is considered to have anticancer effects because of its anti-inflammatory character and further was found to be a negative regulator of angiogenesis.
Formal Description
Interaction-ID: 26084

gene/protein

ADIPOQ

decreases_activity of

process

angiogenesis

Comment Adiponectin is considered to have anticancer effects because of its anti-inflammatory character and further was found to be a negative regulator of angiogenesis.
Formal Description
Interaction-ID: 26085

gene/protein

ADIPOQ

decreases_activity of

disease

Cancer

Comment IL-6 and TNF-alpha are known to promote angiogenesis. The secretion of IL-6 by human adipocytes rises significantly with the BMI. Enhanced levels of IL-6 were found in breast cancer patients.
Formal Description
Interaction-ID: 26086

gene/protein

IL6

increases_activity of

process

angiogenesis

Drugbank entries Show/Hide entries for IL6
Comment IL-6 and TNF-alpha are known to promote angiogenesis. The secretion of IL-6 by human adipocytes rises significantly with the BMI. Enhanced levels of IL-6 were found in breast cancer patients.
Formal Description
Interaction-ID: 26087

gene/protein

TNF

increases_activity of

process

angiogenesis

Drugbank entries Show/Hide entries for TNF
Comment IL-6 and TNF-alpha are known to promote angiogenesis. The secretion of IL-6 by human adipocytes rises significantly with the BMI. Enhanced levels of IL-6 were found in breast cancer patients.
Formal Description
Interaction-ID: 26088

disease

Breast cancer

affects_quantity of

gene/protein

IL6

Drugbank entries Show/Hide entries for IL6
Comment TNF-alpha demonstrates apoptotic effects by inhibiting mTOR and protein synthesis through IkappaB kinase (IKK) and MAPK pathways.
Formal Description
Interaction-ID: 26090

gene/protein

TNF

increases_activity of

Drugbank entries Show/Hide entries for TNF
Comment TNF-alpha demonstrates apoptotic effects by inhibiting mTOR and protein synthesis through IkappaB kinase (IKK) and MAPK pathways.
Formal Description
Interaction-ID: 26091

gene/protein

TNF

decreases_activity of

gene/protein

MTOR

Drugbank entries Show/Hide entries for TNF or MTOR
Comment CRP is associated with an increased risk to develop colorectal, cervical and ovarian cancer.
Formal Description
Interaction-ID: 26092

phenotype

increased circulating C-reactive protein level

increases_activity of

Comment CRP is associated with an increased risk to develop colorectal, cervical and ovarian cancer.
Formal Description
Interaction-ID: 26093

phenotype

increased circulating C-reactive protein level

increases_activity of

disease

Cervical cancer

Comment CRP is associated with an increased risk to develop colorectal, cervical and ovarian cancer.
Formal Description
Interaction-ID: 26094

phenotype

increased circulating C-reactive protein level

increases_activity of

disease

Ovarian cancer

Comment The insulin receptor (IR) with its two subtypes IR-A and IR-B, the insulin growth factor 1 receptor (IGF-IR) and the hybrid receptors (IGF-1R/IR-A and IGF-1R/IR-B) have two extracellular alpha-subunits and two transmembrane beta-subunits that are jointed to each other by disulfide bonds. Insulin binds with high affinity to IR-A or IR-B but has low affinity for IGF-1R, while insulin has no binding to the hybrid receptors. IGF-1 binds to the IGF-1R and to the hybrid receptor IGF-1R/IR-A or IGF-1R/IR-B. IGF-2 binds to IR-A, IGF-1R or to IGF-1R/IR-A hybrid receptor.
Formal Description
Interaction-ID: 26105

complex/PPI

Insulin

increases_activity of

complex/PPI

Insulin receptor subtype A

Comment The insulin receptor (IR) with its two subtypes IR-A and IR-B, the insulin growth factor 1 receptor (IGF-IR) and the hybrid receptors (IGF-1R/IR-A and IGF-1R/IR-B) have two extracellular alpha-subunits and two transmembrane beta-subunits that are jointed to each other by disulfide bonds. Insulin binds with high affinity to IR-A or IR-B but has low affinity for IGF-1R, while insulin has no binding to the hybrid receptors. IGF-1 binds to the IGF-1R and to the hybrid receptor IGF-1R/IR-A or IGF-1R/IR-B. IGF-2 binds to IR-A, IGF-1R or to IGF-1R/IR-A hybrid receptor.
Formal Description
Interaction-ID: 26106

complex/PPI

Insulin

increases_activity of

complex/PPI

Insulin receptor subtype B

Comment The insulin receptor (IR) with its two subtypes IR-A and IR-B, the insulin growth factor 1 receptor (IGF-IR) and the hybrid receptors (IGF-1R/IR-A and IGF-1R/IR-B) have two extracellular alpha-subunits and two transmembrane beta-subunits that are jointed to each other by disulfide bonds. Insulin binds with high affinity to IR-A or IR-B but has low affinity for IGF-1R, while insulin has no binding to the hybrid receptors. IGF-1 binds to the IGF-1R and to the hybrid receptor IGF-1R/IR-A or IGF-1R/IR-B. IGF-2 binds to IR-A, IGF-1R or to IGF-1R/IR-A hybrid receptor.
Formal Description
Interaction-ID: 26107

complex/PPI

Insulin

increases_activity of

complex/PPI

Insulin-like growth factor 1 receptor

with low affinity
Comment The insulin receptor (IR) with its two subtypes IR-A and IR-B, the insulin growth factor 1 receptor (IGF-IR) and the hybrid receptors (IGF-1R/IR-A and IGF-1R/IR-B) have two extracellular alpha-subunits and two transmembrane beta-subunits that are jointed to each other by disulfide bonds. Insulin binds with high affinity to IR-A or IR-B but has low affinity for IGF-1R, while insulin has no binding to the hybrid receptors. IGF-1 binds to the IGF-1R and to the hybrid receptor IGF-1R/IR-A or IGF-1R/IR-B. IGF-2 binds to IR-A, IGF-1R or to IGF-1R/IR-A hybrid receptor.
Formal Description
Interaction-ID: 26108

complex/PPI

Insulin

NOT interacts (colocalizes) with

complex/PPI

INSR-A - IGF1R hybrid complex

Comment The insulin receptor (IR) with its two subtypes IR-A and IR-B, the insulin growth factor 1 receptor (IGF-IR) and the hybrid receptors (IGF-1R/IR-A and IGF-1R/IR-B) have two extracellular alpha-subunits and two transmembrane beta-subunits that are jointed to each other by disulfide bonds. Insulin binds with high affinity to IR-A or IR-B but has low affinity for IGF-1R, while insulin has no binding to the hybrid receptors. IGF-1 binds to the IGF-1R and to the hybrid receptor IGF-1R/IR-A or IGF-1R/IR-B. IGF-2 binds to IR-A, IGF-1R or to IGF-1R/IR-A hybrid receptor.
Formal Description
Interaction-ID: 26109

complex/PPI

Insulin

NOT interacts (colocalizes) with

complex/PPI

INSR-B - IGF1R hybrid complex

Comment The insulin receptor (IR) with its two subtypes IR-A and IR-B, the insulin growth factor 1 receptor (IGF-IR) and the hybrid receptors (IGF-1R/IR-A and IGF-1R/IR-B) have two extracellular alpha-subunits and two transmembrane beta-subunits that are jointed to each other by disulfide bonds. Insulin binds with high affinity to IR-A or IR-B but has low affinity for IGF-1R, while insulin has no binding to the hybrid receptors. IGF-1 binds to the IGF-1R and to the hybrid receptor IGF-1R/IR-A or IGF-1R/IR-B. IGF-2 binds to IR-A, IGF-1R or to IGF-1R/IR-A hybrid receptor.
Formal Description
Interaction-ID: 26110

gene/protein

IGF1

increases_activity of

complex/PPI

Insulin-like growth factor 1 receptor

Drugbank entries Show/Hide entries for IGF1
Comment The insulin receptor (IR) with its two subtypes IR-A and IR-B, the insulin growth factor 1 receptor (IGF-IR) and the hybrid receptors (IGF-1R/IR-A and IGF-1R/IR-B) have two extracellular alpha-subunits and two transmembrane beta-subunits that are jointed to each other by disulfide bonds. Insulin binds with high affinity to IR-A or IR-B but has low affinity for IGF-1R, while insulin has no binding to the hybrid receptors. IGF-1 binds to the IGF-1R and to the hybrid receptor IGF-1R/IR-A or IGF-1R/IR-B. IGF-2 binds to IR-A, IGF-1R or to IGF-1R/IR-A hybrid receptor.
Formal Description
Interaction-ID: 26111

gene/protein

IGF1

increases_activity of

complex/PPI

INSR-A - IGF1R hybrid complex

Drugbank entries Show/Hide entries for IGF1
Comment The insulin receptor (IR) with its two subtypes IR-A and IR-B, the insulin growth factor 1 receptor (IGF-IR) and the hybrid receptors (IGF-1R/IR-A and IGF-1R/IR-B) have two extracellular alpha-subunits and two transmembrane beta-subunits that are jointed to each other by disulfide bonds. Insulin binds with high affinity to IR-A or IR-B but has low affinity for IGF-1R, while insulin has no binding to the hybrid receptors. IGF-1 binds to the IGF-1R and to the hybrid receptor IGF-1R/IR-A or IGF-1R/IR-B. IGF-2 binds to IR-A, IGF-1R or to IGF-1R/IR-A hybrid receptor.
Formal Description
Interaction-ID: 26112

gene/protein

IGF1

increases_activity of

complex/PPI

INSR-B - IGF1R hybrid complex

Drugbank entries Show/Hide entries for IGF1
Comment The insulin receptor (IR) with its two subtypes IR-A and IR-B, the insulin growth factor 1 receptor (IGF-IR) and the hybrid receptors (IGF-1R/IR-A and IGF-1R/IR-B) have two extracellular alpha-subunits and two transmembrane beta-subunits that are jointed to each other by disulfide bonds. Insulin binds with high affinity to IR-A or IR-B but has low affinity for IGF-1R, while insulin has no binding to the hybrid receptors. IGF-1 binds to the IGF-1R and to the hybrid receptor IGF-1R/IR-A or IGF-1R/IR-B. IGF-2 binds to IR-A, IGF-1R or to IGF-1R/IR-A hybrid receptor.
Formal Description
Interaction-ID: 26113

gene/protein

IGF2

increases_activity of

complex/PPI

Insulin-like growth factor 1 receptor

Comment The insulin receptor (IR) with its two subtypes IR-A and IR-B, the insulin growth factor 1 receptor (IGF-IR) and the hybrid receptors (IGF-1R/IR-A and IGF-1R/IR-B) have two extracellular alpha-subunits and two transmembrane beta-subunits that are jointed to each other by disulfide bonds. Insulin binds with high affinity to IR-A or IR-B but has low affinity for IGF-1R, while insulin has no binding to the hybrid receptors. IGF-1 binds to the IGF-1R and to the hybrid receptor IGF-1R/IR-A or IGF-1R/IR-B. IGF-2 binds to IR-A, IGF-1R or to IGF-1R/IR-A hybrid receptor.
Formal Description
Interaction-ID: 26114

gene/protein

IGF2

increases_activity of

complex/PPI

INSR-A - IGF1R hybrid complex

Comment The insulin receptor (IR) with its two subtypes IR-A and IR-B, the insulin growth factor 1 receptor (IGF-IR) and the hybrid receptors (IGF-1R/IR-A and IGF-1R/IR-B) have two extracellular alpha-subunits and two transmembrane beta-subunits that are jointed to each other by disulfide bonds. Insulin binds with high affinity to IR-A or IR-B but has low affinity for IGF-1R, while insulin has no binding to the hybrid receptors. IGF-1 binds to the IGF-1R and to the hybrid receptor IGF-1R/IR-A or IGF-1R/IR-B. IGF-2 binds to IR-A, IGF-1R or to IGF-1R/IR-A hybrid receptor.
Formal Description
Interaction-ID: 26115

gene/protein

IGF2

increases_activity of

complex/PPI

Insulin receptor subtype A

Comment PI3K signaling activates Akt resulting in activation of mTOR and thus, mediating its effects on cell growth by increasing ribosomal protein synthesis and preparation of mitosis through S6k1 and 4E-BP-1. Activation of mTOR results in protein synthesis, cell growth and the preparation of cells for mitosis, all mechanisms that favor tumor growth. Dysregulated signaling of mTOR has been linked to numerous human cancers.
Formal Description
Interaction-ID: 37684

increases_activity of

process

TOR signaling

Comment IL-6 and TNF-alpha are known to promote angiogenesis. The secretion of IL-6 by human adipocytes rises significantly with the BMI. Enhanced levels of IL-6 were found in breast cancer patients.
Formal Description
Interaction-ID: 129691

increases_activity of

process

angiogenesis