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Updated: Mar 25, 2026

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AZGP1 suppresses epithelial-to-mesenchymal transition and hepatic carcinogenesis by blocking TGFβ1-ERK2 pathways

Ming-Yi Xu1, Rong Chen1, Jing-Xia Yu1

  • 1Department of Gastroenterology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.

Cancer Letters
|February 24, 2016
PubMed

Insights

Loss of Zinc-α2-glycoprotein 1 (AZGP1) promotes hepatocellular carcinoma (HCC) invasion by activating TGF-β1-ERK2 signaling. Restoring AZGP1 expression could reverse this process, offering a potential new therapy for HCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Zinc-α2-glycoprotein 1 (AZGP1) is implicated in TGF-β1-induced epithelial-to-mesenchymal transition (EMT).
  • Mechanisms of AZGP1's role in inhibiting EMT and its therapeutic potential in hepatocellular carcinoma (HCC) are not fully understood.

Purpose of the Study:

  • To investigate the role of AZGP1 in inhibiting EMT in HCC.
  • To elucidate the mechanisms underlying AZGP1's function in HCC.
  • To evaluate the therapeutic potential of AZGP1 in HCC.

Main Methods:

  • Examined AZGP1, TGF-β1, and ERK2 expression in HCC patient liver tissues and a rat model.
  • Tested AZGP1's effect on EMT and TGFβ1-ERK2 signaling in human hepatic cancer cells in vitro and in vivo.
  • Administered local AZGP1 mimic injections in a HCC rat model.

Main Results:

  • Hepatic AZGP1 expression was significantly reduced in HCC patients and rats.
  • AZGP1 suppressed EMT by down-regulating mesenchymal markers and up-regulating epithelial markers.
  • AZGP1 blocked TGF-β1-mediated ERK2 phosphorylation, inhibiting cell invasion and EMT in vitro.
  • In vivo AZGP1 mimic injection significantly reduced lung metastasis in HCC.

Conclusions:

  • Loss of AZGP1 facilitates EMT via TGF-β1-ERK2 signaling, promoting HCC invasion.
  • AZGP1 upregulation can reverse EMT and holds promise as a novel therapeutic strategy for HCC.
Keywords:
Epithelial-to-mesenchymal transition (EMT)Extracellular regulated protein kinase 2 (ERK2)Hepatocellular carcinoma (HCC)Transforming growth factor-β1 (TGF-β1)Zinc-α2-glycoprotein 1 (AZGP1)

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