@article{5faa8faad5e34fdf8e9d0a518a4986fd,
title = "Cyfip1 Is a Putative Invasion Suppressor in Epithelial Cancers",
abstract = "Identification of bona fide tumor suppressors is often challenging because of the large number of genetic alterations present in most human cancers. To evaluate candidate genes present within chromosomal regions recurrently deleted in human cancers, we coupled high-resolution genomic analysis with a two-stage genetic study using RNA interference (RNAi). We found that Cyfip1, a subunit of the WAVE complex, which regulates cytoskeletal dynamics, is commonly deleted in human epithelial cancers. Reduced expression of CYFIP1 is commonly observed during invasion of epithelial tumors and is associated with poor prognosis in this setting. Silencing of Cyfip1 disturbed normal epithelial morphogenesis in vitro and cooperated with oncogenic Ras to produce invasive carcinomas in vivo. Mechanistically, we have linked alterations in WAVE-regulated actin dynamics with impaired cell-cell adhesion and cell-ECM interactions. Thus, we propose Cyfip1 as an invasion suppressor gene.",
keywords = "CELLBIO, HUMDISEASE, RNA",
author = "Silva, {Jose M.} and Elena Ezhkova and Javier Silva and Stephen Heart and Mireia Castillo and Yolanda Campos and Veronica Castro and Felix Bonilla and Carlos Cordon-Cardo and Muthuswamy, {Senthil K.} and Scott Powers and Elaine Fuchs and Hannon, {Gregory J.}",
note = "Funding Information: We are especially thankful to Victoria Aranda (CSHL) for help with the 3D model, to Alberto Mu{\v n}oz (Instituto de Investigaciones Biom{\'e}dicas “Alberto Sols”) for providing the Snail expression vector, and to Geraldine Guasch (Rockefeller University) for providing tissue sections of HRas/TGF-β R-II-KO mouse tumors. We also thank June Racelis for help with in situ hybridizations and Nicole Stokes for assistance with skin chamber grafting. We thank Ken Chang and Edie Davis for comments on the manuscript and for helpful discussion. This work was partially supported by the NCI with the K99/R00 project # 54010101-5411 (J.M.S.). G.J.H. and E.F. are Investigators of the Howard Hughes Medical Institute and E.E. is a Life Sciences Foundation Postdoctoral Fellow supported by the New York Stem Cell Institute. This work was supported by grants from the N.I.H (G.J.H. and E.F. R01-AR27883) and by a kind gift from Kathryn W. Davis (G.J.H.). ",
year = "2009",
month = jun,
day = "12",
doi = "10.1016/j.cell.2009.04.013",
language = "English",
volume = "137",
pages = "1047--1061",
journal = "Cell",
issn = "0092-8674",
publisher = "Elsevier B.V.",
number = "6",
}