Research

Life Sciences & Biotechnology

Title :

Ras Effector RASSF10 locks the metabolic reprogramming mechanism in tumour cells

Area of research :

Life Sciences & Biotechnology

Principal Investigator :

Prof. Sundarasamy Mahalingam, Indian Institute Of Technology (IIT) Madras, Tamil Nadu

Timeline Start Year :

2023

Timeline End Year :

2026

Contact info :

Equipments :

Details

Executive Summary :

Tumour development is a complex process with various biological capabilities acquired at each stage. Deregulation in developmental pathways, including RAS, alters cell fate decisions. RASSF10, a member of novel nonenzymatic RAS effectors, is downregulated predominantly through hypermethylation in over 60% of cancers. RASSF10 inhibits cell proliferation, survival, and migration, but its mechanism is yet to be elucidated. High throughput assays have identified nucleolar Guanine nucleotide binding protein Like 3 Like (GNL3L) and Inosine-5?-monophosphate dehydrogenase-2 (IMPDH2) as potential targets of RASSF10. Results from RT-qPCR analysis reveal that RASSF10 downregulates both GNL3L and IMPDH2 expression. GNL3L plays a critical role in normal cellular biology, while IMPDH2 is a critical enzyme for de novo guanine nucleotide biosynthesis. Both GNL3L and IMPDH2 are overexpressed in many solid tumors and negatively correlate with patient survival. The hypothesis is that RASSF10 may control metabolic reprogramming in cancer cells by modulating the expression levels of GNL3L and IMPDH2. The study proposes to characterize the mechanism(s) by which RASSF10 regulates nucleolar function and metabolic programming to control cell proliferation during tumorigenesis and to identify the mechanism by which RASSF10 suppresses GNL3L and IMPDH2 expression in cancers to control nucleolar hypertrophy.

Total Budget (INR):

76,70,237

Organizations involved