Gene interactions and pathways from curated databases and text-mining
J Biol Chem 2009, PMID: 19056742

Insulin receptor substrate-2 regulates aerobic glycolysis in mouse mammary tumor cells via glucose transporter 1.

Pankratz, Shannon L; Tan, Ernest Y; Fine, Yumiko; Mercurio, Arthur M; Shaw, Leslie M

The insulin receptor substrate (IRS) proteins are cytoplasmic adaptor molecules that function as signaling intermediates downstream of activated cell surface receptors. Based on data implicating IRS-2 but not IRS-1 in breast cancer invasion, survival, and metastasis, we assessed the contribution of IRS-1 and IRS-2 to aerobic glycolysis, which is known to impact tumor growth and progression. For this purpose, we used tumor cell lines derived from transgenic mice that express the polyoma virus middle T antigen (PyV-MT) in the mammary gland and that are wild-type (WT) or null for either Irs-1 (Irs-1-/-) or Irs-2 (Irs-2-/-). Aerobic glycolysis, as assessed by the rate of lactic acid production and glucose consumption, was diminished significantly in Irs-2-/- cells when compared with WT and Irs-1-/- cells. Expression of exogenous Irs-2 in Irs-2-/- cells restored the rate of glycolysis to that observed in WT cells. The transcription factor FoxO1 does not appear to be involved in Irs-2-mediated glycolysis. However, Irs-2 does regulate the surface expression of glucose transporter 1 (Glut1) as assessed by flow cytometry using a Glut1-specific ligand. Suppression of Glut1 expression inhibits Irs-2-dependent invasion, which links glycolysis to mammary tumor progression. Irs-2 was shown to be important for mammalian target of rapamycin (mTor) activation, and Irs-2-dependent regulation of Glut1 surface expression is rapamycin-sensitive. Collectively, our data indicate that Irs-2, but not Irs-1, promotes invasion by sustaining the aerobic glycolysis of mouse mammary tumor cells and that it does so by regulating the mTor-dependent surface expression of Glut1.

Diseases/Pathways annotated by Medline MESH: Breast Neoplasms, Neoplasm Invasiveness, Neoplasm Metastasis
Document information provided by NCBI PubMed

Text Mining Data

glucose transporter 1 (Glut1) → Irs-2: " However, Irs-2 does regulate the surface expression of glucose transporter 1 (Glut1) as assessed by flow cytometry using a Glut1-specific ligand "

Glut1 ⊣ Irs-2: " Irs-2 was shown to be important for mammalian target of rapamycin (mTor) activation, and Irs-2 dependent regulation of Glut1 surface expression is rapamycin-sensitive "

mammalian target of rapamycin (mTor) → Irs-2: " Irs-2 was shown to be important for mammalian target of rapamycin (mTor) activation, and Irs-2 dependent regulation of Glut1 surface expression is rapamycin-sensitive "

Glut1 → mTor: " Collectively, our data indicate that Irs-2, but not Irs-1, promotes invasion by sustaining the aerobic glycolysis of mouse mammary tumor cells and that it does so by regulating the mTor dependent surface expression of Glut1 "

Manually curated Databases

No curated data.