Research ArticleCancer

α-Catenin Is a Tumor Suppressor That Controls Cell Accumulation by Regulating the Localization and Activity of the Transcriptional Coactivator Yap1

Sci. Signal.  24 May 2011:
Vol. 4, Issue 174, pp. ra33
DOI: 10.1126/scisignal.2001823

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Crowd Control for Skin Cells

The adhesion protein α epithelial (αE) catenin has been implicated in limiting epithelial cell proliferation under conditions of high cell density (a process called contact inhibition of cell proliferation). Silvis et al. generated mice lacking αE-catenin in hair follicle stem cells and found that they developed squamous cell carcinomas, thus providing genetic evidence that αE-catenin is a tumor suppressor. The authors identified the transcriptional coactivator Yap1 as a protein that interacted with αE-catenin; this interaction inhibited the activity of Yap1 and prevented Yap1 from translocating to the nucleus. Yap1 is also a target for the Hippo signaling pathway, which restricts cell proliferation and organ size by blocking the nuclear translocation of Yap1. In human squamous cell carcinoma tumors, αE-catenin abundance was inversely correlated with Yap1 activation. Thus, αE-catenin may exert its tumor-suppressive effects by sequestering Yap1 and thereby limiting its activity.

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