FPPS mediates TGF-β1-induced non-small cell lung cancer cell invasion and the EMT process via the RhoA/Rock1 pathway

Biochem Biophys Res Commun. 2018 Feb 5;496(2):536-541. doi: 10.1016/j.bbrc.2018.01.066. Epub 2018 Jan 11.

Abstract

Farnesyl pyrophosphate synthase (FPPS), a key enzyme in the mevalonate pathway, was recently shown to play a role in cancer progression. However, its role in non-small cell lung cancer (NSCLC) metastasis and the underlying mechanism remain unclear. In this study, FPPS expression was significantly correlated with TNM stage, and metastasis. Inhibition or knockdown of FPPS blocked TGF-β1-induced cell invasion and epithelial-to-mesenchymal transition (EMT) process. FPPS expression of FPPS was induced by TGF-β1 and FPPS promoted cell invasion and EMT via the RhoA/Rock1 pathway. In conclusion, FPPS mediates TGF-β1-induced lung cancer cell invasion and EMT via the RhoA/Rock1 pathway. These findings suggest new treatment strategies to reduce mortality associated with metastasis in patients with NSCLC.

Keywords: EMT; FPPS; Non-small cell lung cancer; RhoA/Rock1; TGF-β1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Epithelial-Mesenchymal Transition*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Geranyltranstransferase / analysis
  • Geranyltranstransferase / genetics
  • Geranyltranstransferase / metabolism*
  • Humans
  • Lung / metabolism
  • Lung / pathology
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Signal Transduction
  • Transforming Growth Factor beta1 / metabolism*
  • rho-Associated Kinases / metabolism*
  • rhoA GTP-Binding Protein / metabolism*

Substances

  • Transforming Growth Factor beta1
  • Geranyltranstransferase
  • ROCK1 protein, human
  • rho-Associated Kinases
  • rhoA GTP-Binding Protein