YAP Oncogene Overexpression Supercharges Colon Cancer Proliferation

Overview

Journal Cell Cycle

Specialty Cell Biology

Date 2012 Feb 24

PMID 22356765

Citations 73

Authors

Joseph Avruch

Dawang Zhou

Nabeel Bardeesy

Affiliations

Soon will be listed here.

Abstract

The transcriptional co-activator YAP is an evolutionarily conserved regulator of organ size and progenitor cell proliferation. YAP is overexpressed at high frequency in many common human cancers and can directly drive cancer development in mouse models. YAP abundance and nuclear localization are negatively regulated by the Hippo kinase cascade, which, in epithelia, is activated by physiological cell-cell contact. Recent work in intestinal epithelium has established that YAP is constitutively inhibited by the Hippo pathway and entirely dispensable for normal development and homeostasis. YAP serves only in a standby capacity; should cell-cell contact be abrogated, as after intestinal damage, the loss of Hippo input permits increased YAP abundance and nuclear residence. In turn, YAP cooperates with β-catenin to transactivate genes that promote stem cell expansion for epithelial repair. This interplay between overexpressed YAP and β-catenin also drives proliferation of colon cancer cells. The dispensability of YAP in normal intestine makes YAP's expression or outputs attractive targets for cancer therapy.

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