6th RKMVERI Friday Colloquium on “Polyploidy involves the activation of mTORC1 and induces tolerance to glucose starvation” – 13 Jan 2023

We are glad to announce that Ramakrishna Mission Vivekananda Educational and Research Institute (RKMVERI) will be conducting a special colloquium on “Polyploidy involves the activation of mTORC1 and induces tolerance to glucose starvation” on 13 January 2023, 12 noon at Seminar Hall, Narendrapur Campus.

Speaker : Dr. Pushkar Malakar
Co-ordinator: Abhijit Chakrabarti

Polyploidy is the state of a cell or organism having more than two paired sets of chromosomes. Polyploidy is associated with cancers, diabetes, and ageing. Extensive research over several decades have established a central role for mechanistic target of rapamycin (mTOR) in regulating many fundamental cell processes from protein synthesis to autophagy. Deregulated mTOR signaling is implicated in the progression of cancer, diabetes, and ageing process. Even though separately polyploidy and mTOR signaling is associated with cancers, diabetes and ageing, the molecular connection between the two is unknown. The role and implications of mTOR signaling in polyploidy is not studied. Common signaling pathway associated with polyploidy is unspecified. To answer the questions above, we induced polyploidy through several means like treatment with Cytochalasin-B, Colcemid, High Glucose, Nocodazole and Aurora Kinase Inhibitor. Polyploidy was assessed through FACS profile (DNA content >4N), Infrequent cell cycle, multinucleated state, and cellular size. All the methods described, resulted in induction of polyploidy and activation of mTORC1 measured by the phosphorylation status of S6K1 (a bonafide marker of mTORC1). Furthermore, polyploidy induced by Cytochalasin-B and 10X Glucose was greatly reduced upon Torin1(mTORC1 inhibitor) treatment. Activation of mTORC1 pathway in polyploid cells, help them to withstand stress condition (10X Glucose) and proliferate when provided with suitable environment (10X Glucose to Normal media). mTORC1 pathway have been shown to play an important role in controlling autophagy upon glucose starvation. We looked at the fate of normal and polyploid cells upon glucose starvation. Glucose starvation induced severe cell death in normal cells while polyploid cells were tolerant to glucose starvation. Our results reveal a mechanism by which mTORC1 signaling helps polyploid cells. Activation of mTORC1 signaling can serve as a biomarker for polyploid cells. These results suggest that downregulation of mTORC1 in polyploid cells, where mTORC1 is upregulated, should be considered as a new strategy for cancer therapy. Overall, this study will help in the better understanding of polyploidy along with the potential application of treatment in polyploidy related diseases.