Unconventional MAPK-GSK-3β Pathway Behind Atypical Epithelial-Mesenchymal Transition In Hepatocellular Carcinoma

Abstract We recently reported an atypical epithelial mesenchymal transition (EMT) in human hepatoma cell culture Huh7.5, which was non-responsive to the canonical EMT-transcription factors. Here we characterize major pathways regulating this atypical EMT through whole genome transcriptome profiling...

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Autores principales:	Sana Parveen, Dhiviya Vedagiri, Hitha Gopalan Nair, Haripriya Parthasarathy, Krishnan Harinivas Harshan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bc9e9c8636ea40ab9f5d59d854931e02
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spelling	oai:doaj.org-article:bc9e9c8636ea40ab9f5d59d854931e022021-12-02T16:06:52ZUnconventional MAPK-GSK-3β Pathway Behind Atypical Epithelial-Mesenchymal Transition In Hepatocellular Carcinoma10.1038/s41598-017-09179-02045-2322https://doaj.org/article/bc9e9c8636ea40ab9f5d59d854931e022017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09179-0https://doaj.org/toc/2045-2322Abstract We recently reported an atypical epithelial mesenchymal transition (EMT) in human hepatoma cell culture Huh7.5, which was non-responsive to the canonical EMT-transcription factors. Here we characterize major pathways regulating this atypical EMT through whole genome transcriptome profiling and molecular analysis, and identify a unique regulation of EMT by GSK-3β. Our analysis reveals remarkable suppression of several key liver-specific markers in Huh7.5M cells indicating that EMT not only changes the epithelial properties, but alters the characteristics associated with hepatocytes as well. One key finding of this study is that GSK-3β, a known antagonist to β-Catenin signaling and a major pro-apoptotic regulator, is critical for the maintenance of EMT in Huh7.5M cells as its inhibition reversed EMT. Importantly, through these studies we identify that maintenance of EMT by GSK-3β in Huh7.5M is regulated by p38MAPK and ERK1/2 that has not been reported elsewhere and is distinct from another metastatic non-hepatic cell line MDA-MB-231. These data showcase the existence of non-canonical mechanisms behind EMT. The atypicalness of this system underlines the existence of tremendous diversity in cancer-EMT and warrants the necessity to take a measured approach while dealing with metastasis and cancer drug resistance.Sana ParveenDhiviya VedagiriHitha Gopalan NairHaripriya ParthasarathyKrishnan Harinivas HarshanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sana Parveen Dhiviya Vedagiri Hitha Gopalan Nair Haripriya Parthasarathy Krishnan Harinivas Harshan Unconventional MAPK-GSK-3β Pathway Behind Atypical Epithelial-Mesenchymal Transition In Hepatocellular Carcinoma
description	Abstract We recently reported an atypical epithelial mesenchymal transition (EMT) in human hepatoma cell culture Huh7.5, which was non-responsive to the canonical EMT-transcription factors. Here we characterize major pathways regulating this atypical EMT through whole genome transcriptome profiling and molecular analysis, and identify a unique regulation of EMT by GSK-3β. Our analysis reveals remarkable suppression of several key liver-specific markers in Huh7.5M cells indicating that EMT not only changes the epithelial properties, but alters the characteristics associated with hepatocytes as well. One key finding of this study is that GSK-3β, a known antagonist to β-Catenin signaling and a major pro-apoptotic regulator, is critical for the maintenance of EMT in Huh7.5M cells as its inhibition reversed EMT. Importantly, through these studies we identify that maintenance of EMT by GSK-3β in Huh7.5M is regulated by p38MAPK and ERK1/2 that has not been reported elsewhere and is distinct from another metastatic non-hepatic cell line MDA-MB-231. These data showcase the existence of non-canonical mechanisms behind EMT. The atypicalness of this system underlines the existence of tremendous diversity in cancer-EMT and warrants the necessity to take a measured approach while dealing with metastasis and cancer drug resistance.
format	article
author	Sana Parveen Dhiviya Vedagiri Hitha Gopalan Nair Haripriya Parthasarathy Krishnan Harinivas Harshan
author_facet	Sana Parveen Dhiviya Vedagiri Hitha Gopalan Nair Haripriya Parthasarathy Krishnan Harinivas Harshan
author_sort	Sana Parveen
title	Unconventional MAPK-GSK-3β Pathway Behind Atypical Epithelial-Mesenchymal Transition In Hepatocellular Carcinoma
title_short	Unconventional MAPK-GSK-3β Pathway Behind Atypical Epithelial-Mesenchymal Transition In Hepatocellular Carcinoma
title_full	Unconventional MAPK-GSK-3β Pathway Behind Atypical Epithelial-Mesenchymal Transition In Hepatocellular Carcinoma
title_fullStr	Unconventional MAPK-GSK-3β Pathway Behind Atypical Epithelial-Mesenchymal Transition In Hepatocellular Carcinoma
title_full_unstemmed	Unconventional MAPK-GSK-3β Pathway Behind Atypical Epithelial-Mesenchymal Transition In Hepatocellular Carcinoma
title_sort	unconventional mapk-gsk-3β pathway behind atypical epithelial-mesenchymal transition in hepatocellular carcinoma
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/bc9e9c8636ea40ab9f5d59d854931e02
work_keys_str_mv	AT sanaparveen unconventionalmapkgsk3bpathwaybehindatypicalepithelialmesenchymaltransitioninhepatocellularcarcinoma AT dhiviyavedagiri unconventionalmapkgsk3bpathwaybehindatypicalepithelialmesenchymaltransitioninhepatocellularcarcinoma AT hithagopalannair unconventionalmapkgsk3bpathwaybehindatypicalepithelialmesenchymaltransitioninhepatocellularcarcinoma AT haripriyaparthasarathy unconventionalmapkgsk3bpathwaybehindatypicalepithelialmesenchymaltransitioninhepatocellularcarcinoma AT krishnanharinivasharshan unconventionalmapkgsk3bpathwaybehindatypicalepithelialmesenchymaltransitioninhepatocellularcarcinoma
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Unconventional MAPK-GSK-3β Pathway Behind Atypical Epithelial-Mesenchymal Transition In Hepatocellular Carcinoma

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