1. TGM3 promotes epithelial-mesenchymal transition and hepatocellular carcinogenesis and predicts poor prognosis for patients after curative resection.
- Author
-
Hu JW, Yang ZF, Li J, Hu B, Luo CB, Zhu K, Dai Z, Cai JB, Zhan H, Hu ZQ, Hu J, Cao Y, Qiu SJ, Zhou J, Fan J, and Huang XW
- Subjects
- Animals, Carcinogenesis, Carcinoma, Hepatocellular mortality, Carcinoma, Hepatocellular surgery, Cell Line, Tumor, Cell Movement genetics, Cell Proliferation, Female, Gene Expression Regulation, Neoplastic, Humans, Liver Neoplasms mortality, Liver Neoplasms surgery, Male, Mice, Mice, Nude, Middle Aged, Prognosis, Transglutaminases genetics, Xenograft Model Antitumor Assays, Carcinoma, Hepatocellular metabolism, Epithelial-Mesenchymal Transition, Liver Neoplasms metabolism, Signal Transduction, Transglutaminases metabolism
- Abstract
Background: Prognosis of hepatocellular carcinoma (HCC) remains poor despite significant recent improvement in therapy. Recent studies have reported that transglutaminase 3 (TGM3) plays an important role in several human cancer types. However, the role of TGM3 in HCC have not been previously elucidated., Methods: We evaluated the role of TGM3 in regulating HCC cell proliferation, migration, and invasion. We also investigated the prognostic significance of TGM3 in an HCC cohort. Finally, we explored the signalling pathways that TGM3 regulates in HCC., Results: We identified TGM3 to be overexpressed in HCC compared to normal tissues. Higher expression of TGM3 predicts poor prognosis in HCC patients. TGM3 knockdown led to decreased HCC cell proliferation, invasion, and xenograft tumour growth. TGM3 depletion inhibited AKT, extracellular signal-regulated kinase (ERK), p65, and glycogen synthase kinase 3β (GSK3β)/β-catenin activation, but promoted levels of cleaved caspase 3. Moreover, TGM3 knockdown cells had increased E-cadherin levels and decreased vimentin levels, suggesting that TGM3 contributes to epithelial-mesenchymal transition (EMT) in HCC., Conclusion: Our results suggest that TGM3 controls multiple oncogenic pathways in HCC, thereby contributing to increased cell proliferation and EMT, and TGM3 potentially enhances HCC metastasis. TGM3 may serve as a novel therapeutic target in HCC., (Copyright © 2019. Published by Elsevier Ltd.)
- Published
- 2020
- Full Text
- View/download PDF