Research ArticleCancer

The Receptor AXL Diversifies EGFR Signaling and Limits the Response to EGFR-Targeted Inhibitors in Triple-Negative Breast Cancer Cells

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Science Signaling  06 Aug 2013:
Vol. 6, Issue 287, pp. ra66
DOI: 10.1126/scisignal.2004155

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Transactivating Resistance

Resistance to receptor tyrosine kinase (RTK) inhibitors in cancer is often mediated by the activation of alternate receptors that provide compensatory signaling. Meyer et al. showed that the RTK AXL predicts resistance to EGFR (epidermal growth factor receptor) inhibitors in cancer cell lines. Through a ligand-independent mode of transactivation by EGFR, AXL mediated the downstream activation of proteins in a distinct combination, thereby augmenting EGFR signaling and contributing unique output. Diversified, AXL-mediated signaling was required for EGF (epidermal growth factor)–induced migration of TNBC (triple-negative breast cancer) cells. Expression profiles of AXL and EGFR in cancer cell lines predicted resistance to EGFR inhibitors, and treatment with an AXL inhibitor reduced EGFR-elicited proliferation and migration, suggesting that targeting AXL may improve EGFR-targeted drug therapy in TNBC.

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