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Crk and CrkL present with different expression and significance in epithelial ovarian carcinoma
Author(s) -
Wang Jin,
Che Yaling,
Li Gang,
Liu Bin,
Shen Taimin,
Wang Hui,
Linghu Hua
Publication year - 2011
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.20745
Subject(s) - adapter molecule crk , biology , gene knockdown , signal transducing adaptor protein , cancer research , ovarian cancer , carcinogenesis , microbiology and biotechnology , cancer , signal transduction , cell culture , genetics
Adaptor protein Crk and CrkL were thought to be closely related because both consist of one SH2 and two SH3 domains and share 60% homology with the highest identity within their functional domains. Their functions were most presumed to be in part, if not all, redundant. And both were suggested to be implicated in carcinogenesis. In this study, both Crk and CrkL presented with much higher expression in ovarian cancer tissues than those in normal and benign ovarian tissues. However, in contrast with CrkL, high Crk expression displayed close association with advanced stages and high‐grade diseases. Furthermore, the differential binding selectivity of Crk and CrkL to their downstream partners Dock 180 and C3G was demonstrated in ovarian cancer cell line SKOV3 through coimmunoprecipitation. Additionally, Crk‐knockdown cells presented with changed morphology, reduced growth, and cell invasion but remained viable. In contrast, all CrkL‐knockdown cells could not survive over time, gradually detaching from the bottom of plastic dish. In conclusion, these two highly homologous proteins hold features that allow for the differential association with each binding molecules, thereby activating different signaling pathways and being involved in diverse roles in ovarian cancer. Mol. Carcinog. © 2011 Wiley‐Liss, Inc.