Effects of nutrient depletion on translational regulation in HCT-116 Colorectal cancer cells

Date

2024-3-29

Author

MENEMENLİ, NAZLI ŞEVVAL

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Limited nutrient supply in the tumor microenvironment can activate numerous stress response pathways in order to ensure survival. Our research demonstrated that exposing HCT-116 cells to a nutrient-depleted medium containing low glucose, glutamine, and serum for 24 hours led to the inhibition of nutrient sensing pathways such as mTOR, as expected. However, the activation of Ribosomal protein S6 (RPS6), a known target of the mTOR pathway and a component of the small ribosomal subunit was observed. In the absence of an active mTOR pathway, RPS6 was phosphorylated via the MAPK pathway since U0126, a MEK inhibitor could abrogate RPS6 phosphorylation. Analysis of reverse phase protein array (RPPA) data from colorectal tumors showed that the phosphorylation of RPS6 was positively correlated with ERK1/2 phosphorylation. In addition, polysome profiling data demonstrated that nutrient restriction and inhibition of MAPK with U0126 could alter the distribution of ribosomes from polysomes to 80S monosomes, suggesting a role in translational regulation. Overall, our findings suggest that the depletion of nutrients may lead to the simultaneous activation of RPS6 and MAPK pathway as a survival mechanism in HCT-116 colorectal cancer cells.

Subject Keywords

Colorectal cancer, MAPK pathway, mTOR pathway, Nutrient depletion, Translation

URI

https://hdl.handle.net/11511/109381

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Graduate School of Natural and Applied Sciences, Thesis