1. Academic Validation
  2. GP73-mediated secretion of AFP and GP73 promotes proliferation and metastasis of hepatocellular carcinoma cells

GP73-mediated secretion of AFP and GP73 promotes proliferation and metastasis of hepatocellular carcinoma cells

  • Oncogenesis. 2021 Oct 14;10(10):69. doi: 10.1038/s41389-021-00358-3.
Yujuan Liu  # 1 Jiyin Wang  # 1 Ruixiang Yang 1 Yuning Cheng 1 Yue Zhou 1 Hui Li 1 Wei Jiang 1 Xiaowei Zhang 2
Affiliations

Affiliations

  • 1 Department of Biochemistry and Biophysics, School of Basic Medical Sciences, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Peking University Health Science Center, Beijing, PR China.
  • 2 Department of Biochemistry and Biophysics, School of Basic Medical Sciences, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Peking University Health Science Center, Beijing, PR China. xiaoweizhang@bjmu.edu.cn.
  • # Contributed equally.
Abstract

Golgi protein 73 (GP73) and alpha fetoprotein (AFP) serve as biomarkers for the diagnosis of hepatocellular carcinoma (HCC), and their serum levels correlate with patients' outcomes. However, the mechanisms underlying these correlations are unknown. Here we show that GP73 increased the secretion of AFP through direct binding to AFP, thereby promoting the proliferation and metastasis of HCC cells that expressed AFP and its receptor (AFPR). Extracellular GP73 contributed to the proliferation and metastasis of HCC cells independent of AFP and AFPR. Moreover, extracellular AFP and GP73 synergized to enhance the malignant phenotype of HCC cells. Furthermore, extracellular GP73 and AFP inhibited the antitumor effects of sorafenib and synergistically increased the drug resistance of HCC cells. These findings, which reveal the mechanism of GP73-mediated secretion of AFP and its effects on the malignant phenotype of HCC cells, provide a comprehensive theoretical basis for the diagnosis and treatment of HCC and identify potential drug targets.

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