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Owing to the poor clinical outcomes associated with current therapies, the development of novel therapies that target cancer stem cells (CSCs) is desirable. Here, we examined the applicability of our previously established hydrogel\u2010based rapid CSC generation method to human mesothelioma cell lines and further analyzed the characteristics of the induced mesothelioma stem cell (MesoSC) \u2010like cells. Human mesothelioma cell lines cultured on hydrogels presented increased expression of pan\u2010stem cell markers and acquired spheroid formation and early tumorigenicity, suggesting that MesoSC\u2010like cells are highly malignant. Microarray analysis demonstrated that the expression of <jats:italic>SLC13A5<\/jats:italic>, a citrate transporter involved in TCA cycle, was significantly induced in the resulting MesoSC\u2010like cells. The overexpression of SLC13A5 resulted in a metabolic shift toward oxidative phosphorylation, increased phosphorylation of ERK and YAP, and increased SOX2 expression, leading to increased cisplatin resistance. scRNA\u2010seq database analysis revealed that clinical mesothelioma samples contained a small number of SLC13A5\u2010expressing cells. Our findings suggest that the hydrogel\u2010based CSC generation method is also effective for human mesothelioma cells and that SLC13A5 may contribute to MesoSC survival. The new properties of MesoSCs revealed in this study may provide clues for establishing future treatments.<\/jats:p>","DOI":"10.1111\/pin.70001","type":"journal-article","created":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T12:20:57Z","timestamp":1738844457000},"page":"151-165","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["<i>SLC13A5<\/i> plays an essential role in the energy shift to oxidative phosphorylation in cisplatin\u2010resistant mesothelioma stem cells"],"prefix":"10.1111","volume":"75","author":[{"given":"Marie","family":"Kato\u2010Shinomiya","sequence":"first","affiliation":[{"name":"Department of Cancer Pathology, Faculty of Medicine Hokkaido University Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirokazu","family":"Sugino","sequence":"additional","affiliation":[{"name":"Department of Cancer Pathology, Faculty of Medicine Hokkaido University Sapporo 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