Paper Chase is a research database designed to offer abstracts of research articles published in journals that have a highly rated impact factor as determined by ISI Impact Factor and PageRank. Abstracts are organized by date, with the most recently published papers listed first. 

Paper Chase

Cytokinesis failure triggers hippo tumor suppressor pathway activation.

Cell. Aug 14, 2014;158(4):833-48.
Ganem NJ, Cornils H, Chiu SY, O'Rourke KP, Arnaud J, Yimlamai D, Théry M, Camargo FD, Pellman D.

Howard Hughes Medical Institute, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Children's Hospital and Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: david_pellman@dfci.harvard.edu.

Abstract:

Genetically unstable tetraploid cells can promote tumorigenesis. Recent estimates suggest that ∼37% of human tumors have undergone a genome-doubling event during their development. This potentially oncogenic effect of tetraploidy is countered by a p53-dependent barrier to proliferation. However, the cellular defects and corresponding signaling pathways that trigger growth suppression in tetraploid cells are not known. Here, we combine RNAi screening and in vitro evolution approaches to demonstrate that cytokinesis failure activates the Hippo tumor suppressor pathway in cultured cells, as well as in naturally occurring tetraploid cells in vivo. Induction of the Hippo pathway is triggered in part by extra centrosomes, which alter small G protein signaling and activate LATS2 kinase. LATS2 in turn stabilizes p53 and inhibits the transcriptional regulators YAP and TAZ. These findings define an important tumor suppression mechanism and uncover adaptive mechanisms potentially available to nascent tumor cells that bypass this inhibitory regulation.