LATS2 as a poor prognostic marker regulates non-small cell lung cancer invasion by modulating MMPs expression

Biomed Pharmacother. 2016 Aug:82:290-7. doi: 10.1016/j.biopha.2016.04.008. Epub 2016 May 17.

Abstract

Large tumor suppressor 2 (LATS2) plays significant roles in tumorigenesis and cancer progression. This study was aimed to analyze the correlation between LATS2 expression and clinicopathologic features and its prognostic significance in non-small cell lung cancer (NSCLC). LATS2 expression was examined in 73 NSCLC clinical specimens and 22 normal lung tissues using immunohistochemistry. Low levels of LATS2 protein were inversely associated with the T classification (P=0.001), N classification (P=0.005) and clinical stage (P=0.001) in NSCLC patients. Patients with lower LATS2 expression had a significantly shorter overall survival than patients with high LATS2 expression. Multivariate analysis suggested that low expression of LATS2 was an independent prognostic indicator (P=0.002) for the survival of patients with NSCLC. Furthermore, overexpression of LATS2 resulted in mobility inhibition in NSCLC cell lines A549 and H1299, and reduced protein level of matrix metalloproteinase-2 (MMP-2) and MMP-9. On the contrary, LATS2 siRNA treatment enhanced cell mobility and increased MMP-2 and MMP-9 protein expression level. In conclusion, low expression of LATS2 is a potential unfavorable prognostic factor and promoted cell invasion and migration in NSCLC.

Keywords: Invasion; Large tumor suppressor 2; Migration; Non-small cell lung cancer; Prognosis.

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Non-Small-Cell Lung / enzymology*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Lung / pathology
  • Lung Neoplasms / enzymology*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology*
  • Male
  • Matrix Metalloproteinase 2 / metabolism*
  • Matrix Metalloproteinase 9 / metabolism*
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Invasiveness
  • Prognosis
  • Proportional Hazards Models
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • RNA, Small Interfering / metabolism
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Biomarkers, Tumor
  • RNA, Small Interfering
  • Tumor Suppressor Proteins
  • LATS2 protein, human
  • Protein Serine-Threonine Kinases
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9