Role of WIP in metastasis and study of transcriptional regulation of N-Wasp
Amrita S Salvi
Date of Issue2016-05-15
School of Biological Sciences
Tumor cell migration and invasion involves actin cytoskeleton reorganization, which is regulated by N-WASP (Neural-Wiskott Aldrich Syndrome Protein) and its interacting proteins such as WASP interacting protein (WIP). Expression of WIP was found to be higher in metastatic cancer cell line compared to its non-metastatic parental cell line. Overexpression of WIP was found to enhance the proliferative, migratory and invasive ability as well as confer anchorage independent growth properties in A549 lung carcinoma cells indicating a pro-metastatic function of WIP. Expression of N-WASP is enhanced in cells undergoing epithelial mesenchymal transition induced by hypoxia. In order to identify mechanism responsible for the differential expression of N-WASP, the N-WASP promoter was characterized, which led to the identification of HRE (Hypoxia Response element) a regulatory region in N-WASP promoter. Our results suggest that transcription factor HiF1α regulates N-WASP expression in promoting metastasis under hypoxic conditions.