TGF-β2-induced EMT is dampened by inhibition of autophagy and TNF-α treatment

Oncotarget
Subhra DashSudeshna Mukherjee

Abstract

Hepatocellular carcinoma (HCC) typically develops in a chronic inflammatory setting causal to release of a plethora of growth factors and cytokines. However, the molecular effect of these cytokines on HCC progression is poorly understood. In this study, we exposed HCC cells to TGF-β2 (Transforming Growth Factor-β2), which resulted in a significant elevation of EMT (Epithelial to Mesenchymal Transition) like features. Molecular analysis of EMT markers showed an increase at both RNA and protein levels upon TGF-β2 administration along with up-regulation of TGF-β-induced Smad signaling. Induction of EMT was associated with a simultaneous increase in reactive oxygen species (ROS) and cytostasis of TGF-β2-treated cells. Importantly, quenching of ROS resulted in a significant promotion of TGF-β2-induced EMT. Furthermore, cells treated with TGF-β2 also showed an enhanced autophagic flux. Interestingly, inhibition of autophagy by chloroquine-di-phosphate (CQDP) or siRNA-mediated ablation of ATG5 drastically inhibited TGF-β2-induced EMT. Autophagy inhibition significantly increased ROS levels promoting apoptosis. It was further observed that pro-inflammatory cytokine like, TNF-α (Tumor Necrosis Factor-α) can antagonize TGF-β2-induced res...Continue Reading

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Citations

Mar 24, 2018·Cancer Cell International·K LohiteshSudeshna Mukherjee
May 28, 2019·Journal of Experimental & Clinical Cancer Research : CR·Jinguan LinQianjin Liao
Feb 17, 2021·Clinical & Experimental Metastasis·Asha KumariKarthikeyan Mythreye
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Aug 4, 2021·Bone & Joint Research·Mengmeng DuanJing Xie
Aug 28, 2021·Journal of Cellular Physiology·Prashant KumarAmit Mishra
Aug 27, 2021·Frontiers in Cell and Developmental Biology·Bei YinLing Ye
Dec 14, 2021·Frontiers in Cell and Developmental Biology·Suna ZhouYouyou Xie

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Datasets Mentioned

BETA
PRJNA395629

Methods Mentioned

BETA
PCR
flow cytometry
Fluorescent microscopy
lipidation
transcription profiling
fluorescence microscopy

Software Mentioned

ImageJ
CytExpert
Graph Pad Prism
pad Prism
Tophat2
KEGG Pathview
Cuffdiff
Graph
Pathview

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