Dataset Information

Unconventional MAPK-GSK-3? 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 and molecular analysis, and identify a unique regulation of EMT by GSK-3?. 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-3?, a known antagonist to ?-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-3? 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.

SUBMITTER: Parveen S

PROVIDER: S-EPMC5562823 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Parveen Sana S Vedagiri Dhiviya D Nair Hitha Gopalan HG Parthasarathy Haripriya H Harshan Krishnan Harinivas KH

Scientific reports 20170818 1

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 change ...[more]

PMID: 28821798

Similar Datasets

Project description:BackgroundMetastasis and invasion are crucial in determining the mortality of cervical carcinoma (CC) patients. The epithelial-mesenchymal transition (EMT) is now a universal explanation for the mechanisms of tumor metastasis. Α-chimeric protein (α-chimaerin, CHN1) plays an important role in the regulation of signal transduction and development. However, the molecular regulatory relationships between CHN1 and CC progression in relation to EMT have not yet been identified.MethodsThe expression of CHN1 in CC tissues, adjacent tissues, and lymph node metastases from CC patients was detected by immunohistochemistry. Upregulation and knockdown of CHN1 were achieved by transfection of CC cells. The effect of CHN1 on cell proliferation was determined by CCK-8 and plate clone formation assays. Changes in migration and invasion capabilities were evaluated using scratch migration and transwell invasion assays. The effect of CHN1 overexpression and interference on xenograft tumor growth was determined by tumor weight and pathological analyses. The expression of EMT-related mRNAs was measured by qRT-PCR in transfected CC cells. EMT-related proteins and Akt/GSK-3β/Snail signaling pathway-related proteins were also evaluated by western blotting.ResultsCHN1 was overexpressed in CC tissues and was associated with lymph node metastasis and low survival in CC patients. Overexpression of CHN1 promoted cell proliferation, migration, and invasion in CC cells. In contrast, silencing of CHN1 inhibited these phenomena. Overexpression of CHN1 promoted tumor formation in an in vivo xenograft tumor mouse model, with increased tumor volumes and weights. In addition, CHN1 induced the expression of EMT-related transcription factors, accompanied by the decreased expression of epithelial markers and increased expression of mesenchymal markers. The Akt/GSK-3β/Snail signaling pathway was activated by overexpression of CHN1 in vitro, and activation of this pathway was inhibited by the signaling pathway inhibitor LY294002.ConclusionThese results suggest that CHN1 promotes the development and progression of cervical carcinoma via the Akt/GSK-3β/Snail pathway by inducing EMT.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets