Post-Transcriptional Regulation of Rab7a in Lysosomal Positioning and Drug Resistance in Nutrient-Limited Cancer Cells

Güleç Taşkıran AE, Hüsnügil HH, Soltani ZE, Oral G, Menemenli NS, Hampel C, Hübner K, Erlenbach-Wünsch K, Sheraj I, Schneider-Stock R, Akyol A, Liv N, Banerjee S (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Book Volume: 25

Article Number: e12956

Journal Issue: 9

DOI: 10.1111/tra.12956

Abstract

Limited nutrient availability in the tumor microenvironment can cause the rewiring of signaling and metabolic networks to confer cancer cells with survival advantages. We show here that the limitation of glucose, glutamine and serum from the culture medium resulted in the survival of a population of cancer cells with high viability and capacity to form tumors in vivo. These cells also displayed a remarkable increase in the abundance and size of lysosomes. Moreover, lysosomes were located mainly in the perinuclear region in nutrient-limited cells; this translocation was mediated by a rapid post-transcriptional increase in the key endolysosomal trafficking protein Rab7a. The acidic lysosomes in nutrient-limited cells could trap weakly basic drugs such as doxorubicin, mediating resistance of the cells to the drug, which could be partially reversed with the lysosomal inhibitor bafilomycin A1. An in vivo chorioallantoic membrane (CAM) assay indicated a remarkable decrease in microtumor volume when nutrient-limited cells were treated with 5-Fluorouracil (5-FU) and bafilomycin A1 compared to cells treated with either agent alone. Overall, our data indicate the activation of complementary pathways with nutrient limitation that can enable cancer cells to survive, proliferate and acquire drug resistance.

Authors with CRIS profile

Involved external institutions

Middle East Technical University (METU) / Orta Doğu Teknik Üniversitesi Turkey (TR) University Medical Centre Utrecht (UMC Utrecht) Netherlands (NL) Hacettepe University Turkey (TR)

How to cite

APA:

Güleç Taşkıran, A.E., Hüsnügil, H.H., Soltani, Z.E., Oral, G., Menemenli, N.S., Hampel, C.,... Banerjee, S. (2024). Post-Transcriptional Regulation of Rab7a in Lysosomal Positioning and Drug Resistance in Nutrient-Limited Cancer Cells. Traffic (Copenhagen, Denmark), 25(9). https://doi.org/10.1111/tra.12956

MLA:

Güleç Taşkıran, Aliye Ezgi, et al. "Post-Transcriptional Regulation of Rab7a in Lysosomal Positioning and Drug Resistance in Nutrient-Limited Cancer Cells." Traffic (Copenhagen, Denmark) 25.9 (2024).

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