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

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 pr...

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Autores principales: Fan, Jing, Tian, Ruofei, Yang, Xiangmin, Wang, Hao, Shi, Ying, Fan, Xinyu, Zhang, Jiajia, Chen, Yatong, Zhang, Kun, Chen, Zhinan, Li, Ling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9266406/
https://www.ncbi.nlm.nih.gov/pubmed/35805963
http://dx.doi.org/10.3390/ijms23136958
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author Fan, Jing
Tian, Ruofei
Yang, Xiangmin
Wang, Hao
Shi, Ying
Fan, Xinyu
Zhang, Jiajia
Chen, Yatong
Zhang, Kun
Chen, Zhinan
Li, Ling
author_facet Fan, Jing
Tian, Ruofei
Yang, Xiangmin
Wang, Hao
Shi, Ying
Fan, Xinyu
Zhang, Jiajia
Chen, Yatong
Zhang, Kun
Chen, Zhinan
Li, Ling
author_sort Fan, Jing
collection PubMed
description 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.
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spelling pubmed-92664062022-07-09 KCNN4 Promotes the Stemness Potentials of Liver Cancer Stem Cells by Enhancing Glucose Metabolism Fan, Jing Tian, Ruofei Yang, Xiangmin Wang, Hao Shi, Ying Fan, Xinyu Zhang, Jiajia Chen, Yatong Zhang, Kun Chen, Zhinan Li, Ling Int J Mol Sci Article 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. MDPI 2022-06-23 /pmc/articles/PMC9266406/ /pubmed/35805963 http://dx.doi.org/10.3390/ijms23136958 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fan, Jing
Tian, Ruofei
Yang, Xiangmin
Wang, Hao
Shi, Ying
Fan, Xinyu
Zhang, Jiajia
Chen, Yatong
Zhang, Kun
Chen, Zhinan
Li, Ling
KCNN4 Promotes the Stemness Potentials of Liver Cancer Stem Cells by Enhancing Glucose Metabolism
title KCNN4 Promotes the Stemness Potentials of Liver Cancer Stem Cells by Enhancing Glucose Metabolism
title_full KCNN4 Promotes the Stemness Potentials of Liver Cancer Stem Cells by Enhancing Glucose Metabolism
title_fullStr KCNN4 Promotes the Stemness Potentials of Liver Cancer Stem Cells by Enhancing Glucose Metabolism
title_full_unstemmed KCNN4 Promotes the Stemness Potentials of Liver Cancer Stem Cells by Enhancing Glucose Metabolism
title_short KCNN4 Promotes the Stemness Potentials of Liver Cancer Stem Cells by Enhancing Glucose Metabolism
title_sort kcnn4 promotes the stemness potentials of liver cancer stem cells by enhancing glucose metabolism
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9266406/
https://www.ncbi.nlm.nih.gov/pubmed/35805963
http://dx.doi.org/10.3390/ijms23136958
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