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Viral small T oncoproteins transform cells by alleviating hippo-pathway-mediated inhibition of the YAP proto-oncogene

Viral small T oncoproteins transform cells by alleviating hippo-pathway-mediated inhibition of the YAP proto-oncogene

Nguyen, Hung Thanh, Hong, Xin, Tan, Sam, Chen, Qingfeng, Chan, Lifang, Fivaz, Marc ORCID: 0000-0003-1003-7934, Cohen, Stephen M. and Voorhoeve, P. Mathijs (2014) Viral small T oncoproteins transform cells by alleviating hippo-pathway-mediated inhibition of the YAP proto-oncogene. Cell Reports, 8 (3). pp. 707-713. ISSN 2211-1247 (Print), 2211-1247 (Online) (doi:https://doi.org/10.1016/j.celrep.2014.06.062)

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Abstract

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

Item Type: Article
Uncontrolled Keywords: Oncoproteins, Transformation, Hippo pathway, YAP proto-oncogene
Faculty / Department / Research Group: Faculty of Engineering & Science
Faculty of Engineering & Science > Department of Life & Sports Sciences
Last Modified: 28 Nov 2017 15:01
Selected for GREAT 2016: None
Selected for GREAT 2017: None
Selected for GREAT 2018: None
Selected for GREAT 2019: None
URI: http://gala.gre.ac.uk/id/eprint/17889

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