Controlling Ras stability via the Wnt/β-catein signaling: Implication in cancer therapy

5^th World Congress on Cancer Therapy

September 28-30, 2015 Atlanta, USA

Kang-Yell Choi

Translational Research Center for Protein Function Control (TRCP/ ERC), Yonsei University, Korea

Scientific Tracks Abstracts: J Cancer Sci Ther

Abstract :

Three decades after the identification of Ras as an oncogene, the field remains as dynamic and important as ever. Ras controls a wide variety of biological processes including cell growth, survival, and differentiation and is also involved in a number of diseases, including cancer and developmental disorders. However, despite the significant progress that has been made, our understanding of Ras is still incomplete. As adding importance of K-Ras mutation in cancer biology we recently found that oncogenic K-Ras progress tumorigenesis and metastasis of colorectal cancer haboring APC mutations via activating cancer stem cells. Initial activation of �²-catenin by APC loss and further enhancement through K-Ras mutation induces CD44, CD133 and CD166 expression (1). We also provide convincing evidence for a new Ras regulatory mechanism that provides a potential approach for the direct control of Ras instead of the well-known Ras regulation mechanisms of GDP/GTP exchange and the lipid-directed posttranslational modification involved in membrane trafficking. We not only present a detailed mechanism for Ras degradation involving its phosphorylation by negative Wnt/�²-catenin signaling via GSK3�² but also provide critical pathophysiological evidence related to human colorectal cancer (2). The in vivo role of the regulation of Ras stability and the involvement of Ras stabilization in colorectal tumorigenesis were further demonstrated using Adenomatous polyposis coli (Apc)-defective ApcMin/+ and Apc1638N mouse tumours and human colon cancers in various stages, as well as specimens of familial adenomatous polyposis (FAP) caused by Apc mutations. In this meeting, I will also discuss on our current status of the development of anticancer drugs controlling stability of �²-catenin and Ras in control of colorectal cancer.

Biography :

Email: kychoi@yonsei.ac.kr