High FITM2 expression promotes cell migration ability of hepatocellular carcinoma by regulating the formation of caveolae and indicates poor patient survival

Histol Histopathol. 2021 Oct;36(10):1085-1092. doi: 10.14670/HH-18-382. Epub 2021 Oct 21.

Abstract

Background: Hepatocellular carcinoma (HCC) is among the most malignant tumors with high recurrence and low 5-year survival rate. Lipid metabolism is essential in tumor metastasis, although how altered lipid metabolism promotes HCC progression has not been well elucidated. Fat Storage Inducing Transmembrane Protein 2 (FITM2) is a gene involved in lipid homeostasis and cytoskeletal organization; however, its role in regulating tumor biological behavior has not been evaluated.

Methods: In this study, immunohistochemistry was performed to evaluate the expression of FITM2 in HCC. Univariate and multivariate analysis was performed to identify the prognostic factors. RNA interference wound healing and transwell experiments were performed to analyze the biological role of FITM2. Western blot analysis was performed to investigate the potential downstream signaling.

Results: The results revealed that FITM2 was highly expressed in the intratumoral tissues of HCC. Expression of intratumoral FITM2 was associated with microvascular invasion. FITM2 is an independent risk factor of HCC disease-free survival and overall survival. In vitro studies revealed that knockdown of FITM2 significantly inhibited the migration ability of HCC cells. FITM2 promotes HCC cell migration by regulating the expression of caveolin-1 and promoting the formation of caveolae. These results indicate that high intratumoral expression of FITM2 is associated with poor HCC prognosis, which may be applied to develop a new adjuvant therapy.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology*
  • Caveolae / pathology*
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Female
  • Humans
  • Immunohistochemistry
  • Liver Neoplasms
  • Male
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / genetics*
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Prognosis
  • RNA Interference
  • Signal Transduction / genetics
  • Survival Analysis
  • Wound Healing

Substances

  • FITM2 protein, human
  • Membrane Proteins