High glucose induced c-Met activation promotes aggressive phenotype and regulates expression of glucose metabolism genes in HCC cells

Abstract Hepatocellular carcinoma (HCC) is strongly associated with metabolic dysregulations/deregulations and hyperglycemia is a common metabolic disturbance in metabolic diseases. Hyperglycemia is defined to promote epithelial to mesenchymal transition (EMT) of cancer cells in various cancers but...

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Autores principales:	Hande Topel, Ezgi Bağırsakçı, Yeliz Yılmaz, Ayşim Güneş, Gülsün Bağcı, Dehan Çömez, Erkan Kahraman, Peyda Korhan, Neşe Atabey
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e495cb6e91344c98bfe6a3d0b13b04ca
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spelling	oai:doaj.org-article:e495cb6e91344c98bfe6a3d0b13b04ca2021-12-02T15:02:40ZHigh glucose induced c-Met activation promotes aggressive phenotype and regulates expression of glucose metabolism genes in HCC cells10.1038/s41598-021-89765-52045-2322https://doaj.org/article/e495cb6e91344c98bfe6a3d0b13b04ca2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89765-5https://doaj.org/toc/2045-2322Abstract Hepatocellular carcinoma (HCC) is strongly associated with metabolic dysregulations/deregulations and hyperglycemia is a common metabolic disturbance in metabolic diseases. Hyperglycemia is defined to promote epithelial to mesenchymal transition (EMT) of cancer cells in various cancers but its molecular contribution to HCC progression and aggressiveness is relatively unclear. In this study, we analyzed the molecular mechanisms behind the hyperglycemia-induced EMT in HCC cell lines. Here, we report that high glucose promotes EMT through activating c-Met receptor tyrosine kinase via promoting its ligand-independent homodimerization. c-Met activation is critical for high glucose induced acquisition of mesenchymal phenotype, survival under high glucose stress and reprogramming of cellular metabolism by modulating glucose metabolism gene expression to promote aggressiveness in HCC cells. The crucial role of c-Met in high glucose induced EMT and aggressiveness may be the potential link between metabolic syndrome-related hepatocarcinogenesis and/or HCC progression. Considering c-Met inhibition in hyperglycemic patients would be an important complementary strategy for therapy that favors sensitization of HCC cells to therapeutics.Hande TopelEzgi BağırsakçıYeliz YılmazAyşim GüneşGülsün BağcıDehan ÇömezErkan KahramanPeyda KorhanNeşe AtabeyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hande Topel Ezgi Bağırsakçı Yeliz Yılmaz Ayşim Güneş Gülsün Bağcı Dehan Çömez Erkan Kahraman Peyda Korhan Neşe Atabey High glucose induced c-Met activation promotes aggressive phenotype and regulates expression of glucose metabolism genes in HCC cells
description	Abstract Hepatocellular carcinoma (HCC) is strongly associated with metabolic dysregulations/deregulations and hyperglycemia is a common metabolic disturbance in metabolic diseases. Hyperglycemia is defined to promote epithelial to mesenchymal transition (EMT) of cancer cells in various cancers but its molecular contribution to HCC progression and aggressiveness is relatively unclear. In this study, we analyzed the molecular mechanisms behind the hyperglycemia-induced EMT in HCC cell lines. Here, we report that high glucose promotes EMT through activating c-Met receptor tyrosine kinase via promoting its ligand-independent homodimerization. c-Met activation is critical for high glucose induced acquisition of mesenchymal phenotype, survival under high glucose stress and reprogramming of cellular metabolism by modulating glucose metabolism gene expression to promote aggressiveness in HCC cells. The crucial role of c-Met in high glucose induced EMT and aggressiveness may be the potential link between metabolic syndrome-related hepatocarcinogenesis and/or HCC progression. Considering c-Met inhibition in hyperglycemic patients would be an important complementary strategy for therapy that favors sensitization of HCC cells to therapeutics.
format	article
author	Hande Topel Ezgi Bağırsakçı Yeliz Yılmaz Ayşim Güneş Gülsün Bağcı Dehan Çömez Erkan Kahraman Peyda Korhan Neşe Atabey
author_facet	Hande Topel Ezgi Bağırsakçı Yeliz Yılmaz Ayşim Güneş Gülsün Bağcı Dehan Çömez Erkan Kahraman Peyda Korhan Neşe Atabey
author_sort	Hande Topel
title	High glucose induced c-Met activation promotes aggressive phenotype and regulates expression of glucose metabolism genes in HCC cells
title_short	High glucose induced c-Met activation promotes aggressive phenotype and regulates expression of glucose metabolism genes in HCC cells
title_full	High glucose induced c-Met activation promotes aggressive phenotype and regulates expression of glucose metabolism genes in HCC cells
title_fullStr	High glucose induced c-Met activation promotes aggressive phenotype and regulates expression of glucose metabolism genes in HCC cells
title_full_unstemmed	High glucose induced c-Met activation promotes aggressive phenotype and regulates expression of glucose metabolism genes in HCC cells
title_sort	high glucose induced c-met activation promotes aggressive phenotype and regulates expression of glucose metabolism genes in hcc cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e495cb6e91344c98bfe6a3d0b13b04ca
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High glucose induced c-Met activation promotes aggressive phenotype and regulates expression of glucose metabolism genes in HCC cells

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