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Ref Type Journal Article
PMID (23680147)
Authors Jaiswal BS, Kljavin NM, Stawiski EW, Chan E, Parikh C, Durinck S, Chaudhuri S, Pujara K, Guillory J, Edgar KA, Janakiraman V, Scholz RP, Bowman KK, Lorenzo M, Li H, Wu J, Yuan W, Peters BA, Kan Z, Stinson J, Mak M, Modrusan Z, Eigenbrot C, Firestein R, Stern HM, Rajalingam K, Schaefer G, Merchant MA, Sliwkowski MX, de Sauvage FJ, Seshagiri S
Title Oncogenic ERBB3 mutations in human cancers.
Journal Vol Issue Date Pages Journal Short Title
Cancer cell 23 5 2013 May 13 603-17 Cancer Cell
URL
Abstract Text The human epidermal growth factor receptor (HER) family of tyrosine kinases is deregulated in multiple cancers either through amplification, overexpression, or mutation. ERBB3/HER3, the only member with an impaired kinase domain, although amplified or overexpressed in some cancers, has not been reported to carry oncogenic mutations. Here, we report the identification of ERBB3 somatic mutations in ~11% of colon and gastric cancers. We found that the ERBB3 mutants transformed colonic and breast epithelial cells in a ligand-independent manner. However, the mutant ERBB3 oncogenic activity was dependent on kinase-active ERBB2. Furthermore, we found that anti-ERBB antibodies and small molecule inhibitors effectively blocked mutant ERBB3-mediated oncogenic signaling and disease progression in vivo.

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