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Article

KCNN4 Promotes the Stemness Potentials of Liver Cancer Stem Cells by Enhancing Glucose Metabolism

1
Department of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi’an 710005, China
2
Department of Cell Biology, Institutes of Biomedicine, Jinan University, Guangzhou 510632, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Amantini Consuelo and Maria Beatrice Morelli
Int. J. Mol. Sci. 2022, 23(13), 6958; https://doi.org/10.3390/ijms23136958
Received: 30 April 2022 / Revised: 24 May 2022 / Accepted: 20 June 2022 / Published: 23 June 2022
(This article belongs to the Special Issue Tumor Microenvironment and Its Actors: Are Ion Channels Relevant?)
The presence of liver cancer stem cells (LCSCs) is one of the reasons for the treatment failure of hepatocellular carcinoma (HCC). For LCSCs, one of their prominent features is metabolism plasticity, which depends on transporters and ion channels to exchange metabolites and ions. The K+ channel protein KCNN4 (Potassium Calcium-Activated Channel Subfamily N Member 4) has been reported to promote cell metabolism and malignant progression of HCCs, but its influence on LCSC stemness has remained unclear. Here, we demonstrated that KCNN4 was highly expressed in L-CSCs by RT-PCR and Western blot. Then, we illustrated that KCNN4 promoted the stemness of HC-C cells by CD133+CD44+ LCSC subpopulation ratio analysis, in vitro stemness transcription factor detection, and sphere formation assay, as well as in vivo orthotopic liver tumor formation and limiting dilution tumorigenesis assays. We also showed that KCNN4 enhanced the glucose metabolism in LCSCs by metabolic enzyme detections and seahorse analysis, and the KCNN4-promoted increase in LCSC ratios was abolished by glycolysis inhibitor 2-DG or OXPHOS inhibitor oligomycin. Collectively, our results suggested that KCNN4 promoted LCSC stemness via enhancing glucose metabolism, and that KCNN4 would be a potential molecular target for eliminating LCSCs in HCC. View Full-Text
Keywords: LCSCs; KCNN4; metabolism plasticity; glycolysis; OXPHOS LCSCs; KCNN4; metabolism plasticity; glycolysis; OXPHOS
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MDPI and ACS Style

Fan, J.; Tian, R.; Yang, X.; Wang, H.; Shi, Y.; Fan, X.; Zhang, J.; Chen, Y.; Zhang, K.; Chen, Z.; Li, L. KCNN4 Promotes the Stemness Potentials of Liver Cancer Stem Cells by Enhancing Glucose Metabolism. Int. J. Mol. Sci. 2022, 23, 6958. https://doi.org/10.3390/ijms23136958

AMA Style

Fan J, Tian R, Yang X, Wang H, Shi Y, Fan X, Zhang J, Chen Y, Zhang K, Chen Z, Li L. KCNN4 Promotes the Stemness Potentials of Liver Cancer Stem Cells by Enhancing Glucose Metabolism. International Journal of Molecular Sciences. 2022; 23(13):6958. https://doi.org/10.3390/ijms23136958

Chicago/Turabian Style

Fan, Jing, Ruofei Tian, Xiangmin Yang, Hao Wang, Ying Shi, Xinyu Fan, Jiajia Zhang, Yatong Chen, Kun Zhang, Zhinan Chen, and Ling Li. 2022. "KCNN4 Promotes the Stemness Potentials of Liver Cancer Stem Cells by Enhancing Glucose Metabolism" International Journal of Molecular Sciences 23, no. 13: 6958. https://doi.org/10.3390/ijms23136958

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