INVESTIGATION OF THE EFFECTS OF NUTRIENT DEPLETION ON LYSOSOMAL MORPHOLOGY AND TRAFFICKING IN COLORECTAL CANCER CELLS

Date

2023-5-23

Author

Güleç, Aliye Ezgi

Metadata

Show full item record

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Item Usage Stats

134
views

104
downloads

Cite This

Limited nutrient availability in the tumor microenvironment can cause metabolic rewiring of cancer cells which leads to the activation of autophagy confer cells with survival advantages. Our study showed for the first time that incubation of colon cancer cells with a nutrient depleted culture medium containing low glucose, glutamine, and serum resulted in the survival of a population of cells with high viability, accompanied by reduced sensitivity to chemotherapeutic agents. These cells also displayed a remarkable inrease in abundance, size and perinuclear localization of lysosomes. A rapid increase in protein levels of the key endo-lysosomal trafficking protein Rab7a could be implicated in the perinuclar localization of the lysosomes. These perinuclear lysosomes were acidic and could trap weakly basic drugs like doxorubicin, mediating resistance of the cells to the drug, which could be partially reversed with the lysosomotrophic agent Bafilomycin A1. An increase in the multi drug resistance related gene MDR1 was also observed in the nutrient depleted cells, suggesting the presence of multiple mechanisms for drug resistance. Overall, our data suggest that low availability of nutrients may activate various different pathways involving the endolysosomal system to provide cancer cells with survival advantages.

Subject Keywords

Nutrient Depletion, Lysosomal Trapping, Autophagy, Chemoresponse

URI

https://hdl.handle.net/11511/104412

Collections

Graduate School of Natural and Applied Sciences, Thesis