Met is involved in TIGAR-regulated metastasis of non-small-cell lung cancer

Mol Cancer. 2018 May 12;17(1):88. doi: 10.1186/s12943-018-0839-4.

Abstract

TIGAR is a p53 target gene that is known to protect cells from ROS-induced apoptosis by promoting the pentose phosphate pathway. The role of TIGAR in tumor cell invasion and metastasis remains elusive. Here we found that downregulation of TIGAR reduced the invasion and metastasis of NSCLC cells in vitro and in vivo. Immunohistochemical analysis of 72 NSCLC patients showed that TIGAR and Met protein expression was positively correlated with late stages of lung cancer. Besides, patients with high co-expression of TIGAR and Met presented a significantly worse survival. In addition, we found that Met signaling pathway is involved in TIGAR-induced invasion and metastasis. Our study indicates that TIGAR/Met pathway may be a novel target for NSCLC therapy. It is necessary to evaluate the expression of TIGAR before Met inhibitors are used for NSCLC treatment.

Keywords: Epithelial-mesenchymal transition; Met; Metastasis; Non-small-cell lung cancer; TIGAR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Epithelial-Mesenchymal Transition
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Male
  • Mice
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Neoplasm Transplantation
  • Phosphoric Monoester Hydrolases
  • Prognosis
  • Proto-Oncogene Proteins c-met / metabolism*
  • Signal Transduction
  • Survival Analysis
  • Up-Regulation*

Substances

  • Apoptosis Regulatory Proteins
  • Intracellular Signaling Peptides and Proteins
  • MET protein, human
  • Proto-Oncogene Proteins c-met
  • Phosphoric Monoester Hydrolases
  • TIGAR protein, human