Research ArticleCancer

The ErbB4 CYT2 variant protects EGFR from ligand-induced degradation to enhance cancer cell motility

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Science Signaling  19 Aug 2014:
Vol. 7, Issue 339, pp. ra78
DOI: 10.1126/scisignal.2005157

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Drug Resistance Through Dimerization

The epidermal growth factor receptor (EGFR) is often targeted in various cancers, including breast cancer. The EGFR can dimerize with related receptors in the ErbB family, and formation of these heterodimers is associated with the development of resistance to EGFR inhibitors. Kiuchi et al. found that binding of EGFR to a naturally occurring variant of the receptor ErbB4 prevented a ubiquitin E3 ligase from associating with EGFR and triggering its breakdown. The migration of breast cancer cells to EGFR ligands was increased when EGFR was overexpressed with the ErbB4 variant, but not with a mutant that could not dimerize with EGFR. Furthermore, the transcript for this ErbB4 variant was increased in a subset of breast cancer patients.