2. Academic Validation
  3. TM2D1 contributes the epithelial-mesenchymal transition of hepatocellular carcinoma via modulating AKT/β-catenin axis

TM2D1 contributes the epithelial-mesenchymal transition of hepatocellular carcinoma via modulating AKT/β-catenin axis

  • Am J Cancer Res. 2021 Apr 15;11(4):1557-1571.
Jin-Wu Hu 1 2 3,  Yue Yin 1 2 4,  Yang Gao 1 2,  Yan-Yan Nie 5,  Pei-Yao Fu 1 2,  Jia-Bin Cai 1 2,  Kai Zhu 1 2,  Cheng Huang 1 2,  Xiao-Wu Huang 1 2,  Xin-Rong Yang 1 2,  Ya Cao 6 7,  Shuang-Jian Qiu 1 2,  Jia Fan 1 2 8,  Jian Zhou 1 2 8
Affiliations

Affiliations

  • 1 Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University Shanghai 200032, P. R. China.
  • 2 Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education Shanghai 200032, P. R. China.
  • 3 Department of General Surgery, Shanghai Tenth People's Hospital Affiliated with Tongji University 301 Yanchang Road, Shanghai 200072, P. R. China.
  • 4 Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine No. 639 Zhizaoju Road, HuangPu District, Shanghai 200011, P. R. China.
  • 5 Shanghai Lab, Animal Research Center Shanghai 201203, P. R. China.
  • 6 Cancer Research Institute, Xiangya School of Medicine, Central South University Changsha 410078, P. R. China.
  • 7 Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education Changsha 410078, P. R. China.
  • 8 Key Laboratory of Medical Epigenetics and Metabolism, Institute of Biomedical Sciences, Fudan University Shanghai 200032, P. R. China.
PMID: 33948373
Abstract

Various epidemiology studies showed the correlation between Alzheimer's disease (AD) and low incidence of Cancer. However, the etiology underlying etiology of AD-related carcinogenesis remains largely elusive. Our study focused on characterizing the role of TM2D1 (TM2 domain containing 1) in hepatocellular carcinoma. TM2D1 is also known as β-amyloid peptide binding protein and is critical to the pathogenesis of AD. We found that TM2D1 is increasingly expressed in HCC tumors relative to the peritumoral tissues of the matched tumors and high TM2D1 expression predicts unfavorable clinical outcomes. TM2D1 overexpression induced HCC cell proliferation, migration and invasion, which was related to the epithelial-mesenchymal transition (EMT) observed in these cells. Conversely, TM2D1 depletion led to opposite phenotype in HCC. Mechanistically, we found that TM2D1 promoted Akt and β-catenin hyper-activation, which corresponded with molecular marker change in EMT signaling pathway. Taken together, our results indicated that TM2D1 played an important role in the EMT process in HCC cells by activating Akt and β-catenin signaling and may become a promising therapeutic target in HCC.

Keywords

AKT/β-catenin; EMT; Hepatocellular carcinoma; TM2D1; prognostic marker.

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