Research ArticleCancer

Neuregulin 1–activated ERBB4 interacts with YAP to induce Hippo pathway target genes and promote cell migration

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Science Signaling  09 Dec 2014:
Vol. 7, Issue 355, pp. ra116
DOI: 10.1126/scisignal.2005770

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ERBB4 Signals to YAP

Whereas the Hippo pathway limits cell growth in response to mechanical signals or cell-cell contact, growth factors are soluble signals that stimulate cell proliferation. Kinases in the Hippo pathway phosphorylate and inhibit YAP, sequestering YAP in the cytosol and limiting organ size and tissue growth. Neuregulin stimulates the cleavage of the epidermal growth factor receptor family member ERBB4. Haskins et al. found that the cleaved intracellular domain (ICD) of ERBB4 activated YAP-mediated transcription by interacting with YAP. In breast cancer cells, knocking down YAP prevented cell migration induced by neuregulin. These results suggest that in addition to receptor tyrosine kinase signaling, ERBB4 can promote tumor aggressiveness by stimulating YAP.

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