The clinical significance and biological function of large tumour suppressor 2 in hepatocellular carcinoma

Cell Prolif. 2017 Jun;50(3):e12340. doi: 10.1111/cpr.12340. Epub 2017 Mar 1.

Abstract

Objectives: Present evidence has suggested that large tumour suppressor 2 (LATS2) is abnormally expressed in most human cancer. However, the clinical and prognostic value in hepatocellular carcinoma (HCC) is still unknown.

Materials and methods: Large tumour suppressor 2 mRNA and protein expression levels in HCC tissues and cell lines were detected by qRT-PCR, immunohistochemistry or Western blot. The correlation between LATS2 expression and clinicopathological factors was analysed through immunohistochemistry. The function of LATS2 on HCC cell growth and mobility was explored through MTT, colony formation, Transwell migration and invasion assays. The molecular mechanism of LATS2 was screened and confirmed by qRT-PCR and Western blot.

Results and conclusion: In this study, LATS2 mRNA and protein expressions were decreased in HCC tissues and cell lines compared with normal hepatic tissues and hepatic cell line. Low LATS2 expression was oppositely corrected with tumour stage, vascular invasion and metastasis. The univariate and multivariate analyses suggested that low LATS2 expression was an independent poor prognostic factor for HCC patients. The in vitro experiments showed that LATS2 regulated HCC cells migration and invasion, but had no effect on HCC cells proliferation. Meanwhile, LATS2 modulated metastasis-associated genes expression including E-cadherin, vimentin, snail, slug, MMP2 and MMP9. In conclusion, LATS2 is a prognostic biomarker and a tumour metastasis suppressor in HCC.

Keywords: KPM; LATS2; biomarker; hepatocellular carcinoma.

MeSH terms

  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / metabolism*
  • Cell Proliferation
  • Cells, Cultured
  • Female
  • Humans
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / metabolism*
  • Male
  • Middle Aged
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*

Substances

  • RNA, Messenger
  • Tumor Suppressor Proteins
  • LATS2 protein, human
  • Protein Serine-Threonine Kinases