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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\u2010limited cells; this translocation was mediated by a rapid post\u2010transcriptional increase in the key endolysosomal trafficking protein Rab7a. The acidic lysosomes in nutrient\u2010limited 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\u2010limited cells were treated with 5\u2010Fluorouracil (5\u2010FU) 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.<\/jats:p>","DOI":"10.1111\/tra.12956","type":"journal-article","created":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T20:33:08Z","timestamp":1727296388000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Post\u2010Transcriptional Regulation of Rab7a in Lysosomal Positioning and Drug Resistance in Nutrient\u2010Limited Cancer Cells"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1855-1524","authenticated-orcid":false,"given":"Aliye Ezgi","family":"G\u00fcle\u00e7 Ta\u015fk\u0131ran","sequence":"first","affiliation":[{"name":"Department of Biological Sciences Orta Dogu Teknik Universitesi Ankara Turkiye"},{"name":"Department of Molecular Biology and Genetics Ba\u015fkent University Ankara Turkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hep\u015fen H.","family":"H\u00fcsn\u00fcgil","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Orta Dogu Teknik Universitesi Ankara Turkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zahra E.","family":"Soltani","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine University Medical Center Utrecht, Utrecht University Utrecht Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G\u00f6ksu","family":"Oral","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Orta Dogu Teknik Universitesi Ankara Turkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nazl\u0131 S.","family":"Menemenli","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Orta Dogu Teknik Universitesi Ankara Turkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuanpit","family":"Hampel","sequence":"additional","affiliation":[{"name":"Experimental Tumor Pathology, Institute of Pathology University Hospital Erlangen, Friedrich Alexander University Erlangen\u2010N\u00fcrnberg Erlangen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kerstin","family":"Huebner","sequence":"additional","affiliation":[{"name":"Experimental Tumor Pathology, Institute of Pathology University Hospital Erlangen, Friedrich Alexander University Erlangen\u2010N\u00fcrnberg Erlangen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharina","family":"Erlenbach\u2010Wuensch","sequence":"additional","affiliation":[{"name":"Experimental Tumor Pathology, Institute of Pathology University Hospital Erlangen, Friedrich Alexander University Erlangen\u2010N\u00fcrnberg Erlangen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilir","family":"Sheraj","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Orta Dogu Teknik Universitesi Ankara Turkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Regine","family":"Schneider\u2010Stock","sequence":"additional","affiliation":[{"name":"Experimental Tumor Pathology, Institute of Pathology University Hospital Erlangen, Friedrich Alexander University Erlangen\u2010N\u00fcrnberg Erlangen Germany"},{"name":"Comprehensive Cancer Center Erlangen\u2010EMN (CCC ER\u2010EMN) Bavarian Cancer Research Center (BZKF) Erlangen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aytekin","family":"Akyol","sequence":"additional","affiliation":[{"name":"Department of Pathology Hacettepe University Faculty of Medicine Ankara Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2654-9117","authenticated-orcid":false,"given":"Nalan","family":"Liv","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine University Medical Center Utrecht, Utrecht University Utrecht Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4596-6768","authenticated-orcid":false,"given":"Sreeparna","family":"Banerjee","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Orta Dogu Teknik Universitesi Ankara Turkiye"},{"name":"Cancer Systems Biology Laboratory (CanSyL) Orta Dogu Teknik Universitesi Ankara Turkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,9,23]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-092910-154237"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.14348\/molcells.2016.0310"},{"issue":"324","key":"e_1_2_8_4_1","first-page":"1029","article-title":"Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation","volume":"2009","author":"Heiden M. 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