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IFITM3 promotes hepatocellular carcinoma invasion and metastasis by regulating MMP9 through p38/MAPK signaling

Jiaqi Min1, Qian Feng2, Wenjun Liao1

  • 1Department of General Surgery the Second Affiliated Hospital of Nanchang University China.

FEBS Open Bio
|August 9, 2018
PubMed

Insights

Interferon-induced transmembrane protein 3 (IFITM3) promotes hepatocellular carcinoma (HCC) metastasis by upregulating MMP9 via the p38/MAPK pathway. Targeting this IFITM3-MMP9 axis may offer new strategies for treating invasive HCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Interferon-induced transmembrane protein 3 (IFITM3) is overexpressed in various cancers.
  • The specific role of IFITM3 in hepatocellular carcinoma (HCC) metastasis remains unclear.

Purpose of the Study:

  • To investigate the function and mechanism of IFITM3 in HCC metastasis.
  • To determine the correlation between IFITM3 expression, metastasis, and prognosis in HCC patients.

Main Methods:

  • Analysis of IFITM3 expression in HCC tissues versus adjacent non-tumor tissues.
  • In vitro and in vivo experiments involving IFITM3 knockdown and MMP9 manipulation.
  • Investigation of the p38/MAPK signaling pathway.

Main Results:

  • IFITM3 was frequently overexpressed in HCC and correlated with metastasis and poor prognosis.
  • IFITM3 knockdown inhibited HCC invasion and metastasis, reducing MMP9 expression.
  • MMP9 upregulation rescued, while MMP9 knockdown attenuated, IFITM3-mediated HCC cell migration and invasion.
  • IFITM3 regulates MMP9 via the p38/MAPK pathway.

Conclusions:

  • A novel regulatory circuit involving IFITM3, p38/MAPK, and MMP9 was identified in HCC.
  • Dysregulation of this IFITM3-p38/MAPK-MMP9 pathway contributes to HCC invasiveness and metastasis.
Keywords:
IFITM3MMP9hepatocellular carcinomametastasisp38/MAPK pathway

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