Regulatory System of Anchorage-Dependent Cell Growth

点击翻译按钮获取中文摘要

The core feature of cancer is so-called "uncontrolled growth of cell". This unique growth property of cancer cells can be reproduced as "the anchorage-independent growth of cell" in the in vitro cell culture system. This feature, in other word, suggests the presence of highly organized control system of cell growth that requires the attachment of cells to the substratum. The progress of molecular biology enabled us to understand the principal mechanism of growth control by the growth factors. In contrast, the mechanism of "the anchorage-independent growth" that distinguishes cancer cells from its parental normal cells is yet largely unclear. This project aimed to identify the signaling pathways critical for the anchorage-independent growth with our originally developed materials and methods. With normal and transformed cells cultured in attached or suspended conditions, we analyzed the change in the feature of growth signaling. Focusing on the important signaling molecules, we developed their dominant negative forms and siRNAs. With these tools, we characterized the uniqueness of tumor-specific cell growth. By our study, involvement of several important signaling molecules such as SHPS-1, Stat3, Ras and FAK in tumor-specific growth was demonstrated. In addition, we showed that SHPS-1/SHP-2 signaling positively drived the growth of normal cells in attached condition, and activated the invasiveness of cancer cells. Moreover, we found that normal cells in suspended condition were undergone apoptosis that required caspase system. Identification of signaling that control the anchorage-dependent apoptosis is an important problem to be clarified.