Functional Genomics Approach Identifies Novel Signaling Regulators of TGFα Ectodomain Shedding.

ABSTRACT: Ectodomain shedding of cell-surface precursor proteins by metalloproteases generates important cellular signaling molecules. Of importance for disease is the release of ligands that activate the EGFR, such as TGFα, which is mostly carried out by ADAM17 [a member of the A-disintegrin and metalloprotease (ADAM) domain family]. EGFR ligand shedding has been linked to many diseases, in particular cancer development, growth and metastasis, as well as resistance to cancer therapeutics. Excessive EGFR ligand release can outcompete therapeutic EGFR inhibition or the inhibition of other growth factor pathways by providing bypass signaling via EGFR activation. Drugging metalloproteases directly have failed clinically because it indiscriminately affected shedding of numerous substrates. It is therefo

SUBMITTER: Wilson JL 

PROVIDER: S-EPMC5859574 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature