open access

https://hdl.handle.net/2115/97461

SLC13A5 plays an essential role in the energy shift to oxidative phosphorylation in cisplatin-resistant mesothelioma stem cells

英語

Reprogramming

2025-02-06

John Wiley & Sons

Pathology international

75(3)

151-165

Mesothelioma is a highly aggressive tumor affecting an increasing number of patients worldwide. 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-based rapid CSC generation method to human mesothelioma cell lines and further analyzed the characteristics of the induced mesothelioma stem cell (MesoSC) -like cells. Human mesothelioma cell lines cultured on hydrogels presented increased expression of pan-stem cell markers and acquired spheroid formation and early tumorigenicity, suggesting that MesoSC-like cells are highly malignant. Microarray analysis demonstrated that the expression of SLC13A5, a citrate transporter involved in TCA cycle, was significantly induced in the resulting MesoSC-like 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-seq database analysis revealed that clinical mesothelioma samples contained a small number of SLC13A5-expressing cells. Our findings suggest that the hydrogel-based 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.

学術雑誌論文

Accepted Manuscript

This is the peer reviewed version of the following article: Kato-Shinomiya M, Sugino H, Wang L, Saito Y, He J, Tanei Z-i, et al. SLC13A5 plays an essential role in the energy shift to oxidative phosphorylation in cisplatin-resistant mesothelioma stem cells. Pathol Int. 2025; 75: 151–165, which has been published in final form at https://doi.org/10.1111/pin.70001. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.

1320-5463

1440-1827