5th World Congress on Cancer Therapy
Yonsei University, Korea
Title: Controlling Ras stability via the Wnt/-catein signaling: Implication in cancer therapy
Biography: Kang-Yell Choi
Three decades aft er the identifi cation of Ras as an oncogene, the fi eld remains as dynamic and important as ever. Ras controls a wide variety of biological processes including cell growth, survival, and diff erentiation and is also involved in a number of diseases, including cancer and developmental disorders. However, despite the signifi cant 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 β-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 modifi cation involved in membrane traffi cking. We not only present a detailed mechanism for Ras degradation involving its phosphorylation by negative Wnt/β-catenin signaling via GSK3β but also provide critical pathophysiological evidence related to human colorectal cancer (2). Th e 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 β-catenin and Ras in control of colorectal cancer.