Novel Tumour Supressor mechanisms
04 Mar 2016
Novel tumour supressor pathways involving PTEN
Dr Subba Reddy Maddika, Intermediate Fellow, CDFD, Hyderabad
PTEN (phosphatase and tensin homologue deleted on chromosome 10) is an important tumor suppressor protein that is lost or mutated in various cancers such as glioblastomas, endometrial carcinomas, breast carcinomas, and prostate carcinomas. So far, the tumor suppressor function of PTEN is mainly attributed to its functional ability of removing phosphate group from a lipid phosphatidylinositol-3,4,5-trisphosphate (PIP3) present at the cell membrane. Removal of phosphate from PIP3 blocks the proliferative signals. In this work, we show alternate mechanisms of how PTEN may act as a tumor suppressor. We demonstrated that PTEN removes phosphate group from RAB7 protein and regulates its localization to the late endosomal membranes. Rab7 is a central player in the endocytic pathway, where it governs the transition of early to late endosomes followed by their fusion with lysosomes. Proper Rab7 localization on endosomes is required for efficient degradation of growth factor receptors by lysosomes. Thus, by guiding Rab7 localization on to endosomes, PTEN promotes the degradation of growth factors through endosome maturation and blocks the proliferative signaling.
Image: Increased accumulation of EGF (epidermal growth factor) in early endosomes (EEA1 positive) in PTEN depleted cells compared to control cells.