Insulin receptor substrate regulation of phosphoinositide 3-kinase.
Insulin receptor substrates (IRS) serve as downstream messengers from activated cell surface receptors to numerous signaling pathway cascades. One of these pathways, phosphoinositide 3-kinase (PI3K), frequently displays aberrant function in the setting of cancer. IRS proteins are capable of both regulating and activating PI3K, depending on the cell of origin. As such, both prohost and protumor functions have been described for IRS proteins in human cancers. IRS proteins may eventually serve as biomarkers of PI3K activity, and serve a much-needed role as a guide to using targeted pathway therapy. Additionally, IRS-1 could be indirectly targeted in lung cancer, by inhibiting neutrophil elastase, which functions to degrade IRS-1 in lung tumor cells, thereby generating PI3K hyperactivity.
Metz
Heather E
HE
Department of Medicine, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
Houghton
A McGarry
AM
D019870:1-Phosphatidylinositol 4-Kinase / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000502:physiology*; D019272:Leukocyte Elastase / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism*; D015398:Signal Transduction
D055504:Insulin Receptor Substrate Proteins; D019870:1-Phosphatidylinositol 4-Kinase; D019272:Leukocyte Elastase