Molecular Pathways: Receptor Ectodomain Shedding in Treatment, Resistance, and Monitoring of Cancer.

ABSTRACT: Proteases known as sheddases cleave the extracellular domains of their substrates from the cell surface. The A Disintegrin and Metalloproteinases ADAM10 and ADAM17 are among the most prominent sheddases, being widely expressed in many tissues, frequently overexpressed in cancer, and promiscuously cleaving diverse substrates. It is increasingly clear that the proteolytic shedding of transmembrane receptors impacts pathophysiology and drug response. Receptor substrates of sheddases include the cytokine receptors TNFR1 and IL6R; the Notch receptors; type-I and -III TGFβ receptors; receptor tyrosine kinases (RTK) such as HER2, HER4, and VEGFR2; and, in particular, MET and TAM-family RTKs AXL and Mer (MerTK). Activation of receptor shedding by mechanical cues, hypoxia, radiation, and phosphosig

SUBMITTER: Miller MA 

PROVIDER: S-EPMC5290119 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature