Life Sciences & Biotechnology
Title : | Cell-matrix adhesion-dependent Golgi organisation: Regulation and role in normal and anchorage-independent cancers. |
Area of research : | Life Sciences & Biotechnology |
Focus area : | Cancer Biology, Cell Adhesion |
Principal Investigator : | Dr. Nagaraj Balasubramanian, Indian Institute of Science Education and Research (IISER) Pune, Maharashtra |
Timeline Start Year : | 2023 |
Timeline End Year : | 2026 |
Contact info : | nagaraj@iiserpune.ac.in |
Details
Executive Summary : | The adhesion of cells to the extracellular matrix (ECM) is crucial for membrane trafficking and anchorage-dependent signaling in cells. Loss of adhesion triggers caveolar endocytosis and exocyst dependent exocytosis, which are deregulated in cancers to support anchorage-independence. Golgi organization and function are closely controlled in normal cells and deregulated in diseases like anchorage-independent cancers. Integrin-mediated adhesion is a novel regulator of Golgi organization and function. Loss of adhesion disorganizes Golgi in anchorage-dependent mouse fibroblasts, human fibroblasts, and endothelial cells. Golgi integrity is restored upon re-adhesion to fibronectin and disrupted by integrin blocking antibody. The loss of adhesion mediated Golgi disorganisation provides a unique opportunity to understand the regulation of Golgi compartments. Differential Arf1 activation in cis-medial vs trans-Golgi compartments in suspended cells could be mediated by the differential recruitment of Arf1 GEFs (BIG1/2 or GBF). Using inhibitors to target these could affect Golgi organization. Differential Arf1 activation could also be reflected in how plus-end motor protein kinesins are recruited to regulate Golgi compartments, possibly mediated by microtubule stability. Loss of adhesion mediated Golgi disorganisation affects Golgi function, regulating cell surface glycosylation in an Arf1-dependent manner. Anchorage-independent cancers are defective in their Golgi organization and function, resulting in distinct changes in their glycosylation profile. Gene expression and Golgi proteomic profile will be used to identify regulators and test their effect on Golgi organization and function. |
Co-PI: | Dr. Mallur Srivatsan Madhusudhan, Indian Institute of Science Education and Research (IISER) Pune, Maharashtra-411008 |
Total Budget (INR): | 58,88,696 |
Organizations involved