Cleavage of p130Cas in anoikis

✍ Scribed by Lin Wei; Yu Yang; Xing Zhang; Qiang Yu

• Book ID: 102302523
• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 287 KB
• Volume: 91
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.10760

✦ Synopsis

Abstract

p130^Cas^ is a multifunctional signaling adaptor protein. It integrates and relays signals generated from a variety of extracellular stimuli and regulates a number of cellular activities including cell death. In this study, we analyzed the regulation and function of p130^Cas^ in anoikis, a type of apoptosis caused by disruption of cell‐matrix interactions. We found that p130^Cas^ was specifically cleaved during anoikis in anoikis‐sensitive epithelial cells, but not in anoikis‐resistant tumor cells. There is a close correlation between p130^Cas^ cleavage and anoikis. Furthermore, we found that the cleavage of p130^Cas^, as well as another focal adhesion component FAK, is different from that of caspase substrate PARP and spectrin. Although caspases and calpain were found to be involved in the cleavage of p130^Cas^, there appear to be other unidentified proteases that are mainly responsible for the cleavage of p130^Cas^, particularly at the early stage of anoikis. Overexpression of the p130^Cas^ cleavage product induced apoptosis. Taken together, these data suggest that there are novel proteases involved in the cleavage of p130^Cas^ during anoikis, which may be functionally involved in the onset of anoikis. p130^Cas^ may have a dual role in the regulation of anoikis. On one hand, it mediates a survival signal from cell‐matrix interactions when cells are attached to the extracellular matrix. On the other hand, it participates in executing cell death when cell‐matrix interactions are disrupted. These observations provide new insights into the understanding of the function of p130^Cas^ and the molecular mechanism of anoikis. © 2003 Wiley‐Liss, Inc.