Cyfip1 Is a Putative Invasion Suppressor in Epithelial Cancers

Silva, J. M., Ezhkova, E., Silva, J., Heart, S., Castillo, M., Campos, Y., Castro, V., Bonilla, F., Cordon-Cardo, C., Muthuswamy, S. K., Powers, S., Fuchs, E., Hannon, G. J. (2009) Cyfip1 Is a Putative Invasion Suppressor in Epithelial Cancers. Cell, 137 (6). pp. 1047-1061. ISSN 00928674 (ISSN)

DOI: 10.1016/j.cell.2009.04.013


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. © 2009 Elsevier Inc. All rights reserved.

Item Type: Paper
Uncontrolled Keywords: CELLBIO HUMDISEASE RNA actin protein Cyfip1 protein subunit Ras protein short hairpin RNA tumor suppressor protein unclassified drug animal experiment animal model article cancer invasion cell adhesion controlled study cytoskeleton epithelium tumor extracellular matrix gene deletion gene silencing genetic analysis genome analysis human human cell in vitro study in vivo study invasive carcinoma morphogenesis mouse nonhuman priority journal prognosis protein analysis protein expression protein function protein protein interaction regulatory mechanism RNA interference tumor suppressor gene Adaptor Proteins, Signal Transducing Animals Carcinoma Cell Line, Tumor Cells, Cultured Epithelial Cells Gene Expression Profiling Gene Expression Regulation, Neoplastic Humans Keratinocytes Mice Neoplasm Invasiveness Neoplasm Transplantation Transplantation, Heterologous
Subjects: diseases & disorders > cancer
diseases & disorders
diseases & disorders > cancer > cancer types
CSHL Authors:
Communities: CSHL labs > Hannon lab
CSHL labs > Powers lab
CSHL Cancer Center Shared Resources > Bioinformatics Service
Depositing User: Matt Covey
Date: 2009
Date Deposited: 09 Jan 2013 16:44
Last Modified: 30 Dec 2014 15:39
PMCID: PMC2754270
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