Role of PTB and CXCR4 in Colon Cancer Progression and Metastasis

Colorectal cancer ranks second as a cause of death due to cancer in the United States. Every year 160,000 cases of colorectal cancer are diagnosed, and 57,000 patients die. Colon cancer begins as a benign adenomatous polyp, and it slowly progresses into an advanced adenoma with high-grade dysplasia and then becomes invasive cancer. The challenges in the fight against colon cancer are to understand the molecular basis of the susceptibility to colorectal cancer and to determine factors that initiate the development of the tumor, drive its progression, in addition to its responsiveness or resistance to anti-tumor agents. One focus of our research is to characterize the molecular mechanisms leading to the initiation and progression of colorectal cancers. Towards this goal we have demonstrated that posttranscriptional regulation of gene expression at the level of mRNA stability and translation plays a critical role in carcinogenesis. RNA binding proteins, through binding to specific sequences in the mRNA can increase the stability and, or translation of mRNA, leading to over-expression of the protein encoded by the mRNA. In this proposal, we will focus on RNA binding protein PTB (Polyryrimidine Tract Binding Protein) and its role in regulating the stability and translation of the chemokine receptor CXCR4, a critical player in tumor metastasis. The proposed studies could identify the role of PTB in regulating CXCR4 expression in colon cancer cells. Furthermore, these studies will give us the necessary preliminary proof to further expand the investigations into understanding the role of PTB and CXCR4 in tumor progression.