The cancer cell biology of the integral membrane protein CUB domain containing protein 1(CDCP1)

CUB domain containing protein 1 (CDCPl) is an integral membrane glycoprotein that has been implicated in the metastasis of lung cancer, gastric cancer and melanoma. The hypothesis ofthis study was that CDCPl also played a role in colon cancer. This was primarily tested using human colon cancer cell lines. The nature of the CDCP 1 protein, and its localisation had not been studied in colon cancer cells. The first stage of the investigation was therefore to characterise the CDCPl protein in colon cancer cell lines. Previous studies have suggested that CDCPl and the tetraspanin CD9 associate within membrane-associated, tetraspanin-enriched microdomains (TEMs). Evidence consistent with this is presented herein. In addition to the expected plasma membrane localisation of CDCPl, ajuxtanuclear pool ofCDCPl was present in SW480 colon cancer cells. A high molecular mass (HMM)-CDCP 1 protein species was described that may result from CDCPl dimerisation. TEM associated CDCPl, juxtanuclear CDCPl, and HMM-CDCPl may be involved in the cancer-associated functions of CD CPl. The second part of the study aimed to assess the phenotypic effect of CDCP 1 expression on colon cancer cell lines. Uncontrolled growth is a hallmark of cancer. The effect of CDCP 1 on colon cancer cell growth was investigated, however CDCP I was not found to promote the growth ofSW480 colon cancer cells. Given CDCPl 's role in promoting the metastasis of other cancers, the effect of modulating CDCP 1 expression on colon cancer cell line adhesion and motility was assessed. CDCPl expression modulated cell-substratum adhesion in a cell line-dependent manner. Reduction of CDCP 1 expression in SW 480 colon cancer cells reduced their chemotactic motility. These results are consistent with a role for CDCPl in promoting a cellular phenotype that could facilitate the metastasis of colon cancer. If CDCP 1 expression were shown to promote colon cancer metastasis in an animal model, CDCPl could provide an important target for the development of anti-metastatic therapeutics for colon cancer patients.EThOS - Electronic Theses Online ServiceGBUnited Kingdo