Understanding the role of nuclear membrane associated proteins under differential flow dynamics driving EMT and survival of tumor cells
Implementing Organization
Birla Institute of Technology and Science
Principal Investigator
Dr. Sudeshna Mukherjee
Birla Institute Of Technology And Science (BITS), Pilani, Rajasthan
CO-Principal Investigator
Dr. Suvanjan Bhattacharyya
Birla Institute Of Technology And Science (BITS), Pilani, Rajasthan-333031, Dr. Venkatesh KP Rao, Birla Institute Of Technology And Science (BITS), Pilani, Rajasthan-333031
Project Overview
Tumor cells often disseminate and enter the bloodstream, encountering haemodynamic forces influenced by blood flow patterns and vessel geometry. To counter this, they respond to mechanical cues and alter their physical and molecular properties. In a study, human hepatocellular carcinoma (HCC) cells were subjected to flow dynamics and found to show increased expression of markers associated with epithelial to mesenchymal transition (EMT), which facilitates invasive properties of tumor cells. Under flow, HCC cells under flow showed distinct changes in nuclear dimensions. Recent literature suggests that nuclear membrane associated proteins (NMAPs) like LINC and lamins can act as effective mechano-transducers, promoting survival and cellular differentiation event- EMT. Targeting NMAPs may hold promise in attenuating tumor cell invasive properties. The study plans to fabricate, design, and simulate microfluidic flow systems resembling circulatory vessels, analyze the effect of flow on LINC and lamins, and evaluate the role of differentially regulated NMAPs in controlling flow-induced EMT through modulation of chromatin associated domains. This integrated approach could provide a strong base for future diagnostic and therapeutic opportunities.
Source
Source
Anusandhan National Research Foundation/Science and Engineering Research Board (SERB), DST 2023-24
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