Viral Small T Oncoproteins Transform Cells by Alleviating Hippo-Pathway-Mediated Inhibition of the YAP Proto-oncogene

• DOI: 10.1016/j.celrep.2014.06.062
• Publication Date: 2014-07-31T15:47:42Z
• Authors: Hung Thanh Nguyen; Xin Hong; Sam Tan; Qingfeng Chen; Lifang Chan; Marc Fivaz; Stephen M. Cohen; P. Mathijs Voorhoeve
• Keywords: Hippo signaling pathway

Primary human cells can be transformed into tumor by a defined set of genetic alterations including telomerase, oncogenic RasV12, and the suppressors p53 pRb. SV40 small T (ST) is required for anchorage-independent growth in vitro vivo. Here, we identify Hippo suppressor pathway as critical target ST cellular transformation. We report that uncouples YAP from inhibitory activity through PAK1-mediated inactivation NF2. Membrane-tethered activated PAK sufficient to bypass requirement growth. acts via mediate transforming effects ST. Activation endogenous ST-mediated transformation xenograft formation. Our findings uncover final gatekeeper tumorigenesis primary cells.