Clinical & Experimental Metastasis

, Volume 31, Issue 6, pp 613–623

FN14 expression correlates with MET in NSCLC and promotes MET-driven cell invasion

  • Timothy G. Whitsett
  • Shannon P. Fortin Ensign
  • Harshil D. Dhruv
  • Landon J. Inge
  • Paul Kurywchak
  • Kerri K. Wolf
  • Janine LoBello
  • Christopher B. Kingsley
  • Jeffrey W. Allen
  • Glen J. Weiss
  • Nhan L. Tran
Research Paper

DOI: 10.1007/s10585-014-9653-6

Cite this article as:
Whitsett, T.G., Fortin Ensign, S.P., Dhruv, H.D. et al. Clin Exp Metastasis (2014) 31: 613. doi:10.1007/s10585-014-9653-6

Abstract

The five-year survival rate in advanced non-small cell lung cancer (NSCLC) remains below ten percent. The invasive and metastatic nature of NSCLC tumor cells contributes to the high mortality rate, and as such the mechanisms that govern NSCLC metastasis is an active area of investigation. Two surface receptors that influence NSCLC invasion and metastasis are the hepatocyte growth factor receptor (HGFR/MET) and fibroblast growth factor-inducible 14 (FN14). MET protein is over-expressed in NSCLC tumors and associated with poor clinical outcome and metastasis. FN14 protein is also elevated in NSCLC tumors and positively correlates with tumor cell migration and invasion. In this report, we show that MET and FN14 protein expressions are significantly correlated in human primary NSCLC tumors, and the protein levels of MET and FN14 are elevated in metastatic lesions relative to patient-matched primary tumors. In vitro, HGF/MET activation significantly enhances FN14 mRNA and protein expression. Importantly, depletion of FN14 is sufficient to inhibit MET-driven NSCLC tumor cell migration and invasion in vitro. This work suggests that MET and FN14 protein expressions are associated with the invasive and metastatic potential of NSCLC. Receptor-targeted therapeutics for both MET and FN14 are in clinical development, the use of which may mitigate the metastatic potential of NSCLC.

Keywords

Non-small cell lung cancer MET FN14 Metastasis 

Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Timothy G. Whitsett
    • 1
  • Shannon P. Fortin Ensign
    • 1
    • 2
  • Harshil D. Dhruv
    • 1
  • Landon J. Inge
    • 3
  • Paul Kurywchak
    • 1
  • Kerri K. Wolf
    • 1
  • Janine LoBello
    • 4
  • Christopher B. Kingsley
    • 5
  • Jeffrey W. Allen
    • 6
  • Glen J. Weiss
    • 1
    • 7
  • Nhan L. Tran
    • 1
  1. 1.Cancer and Cell Biology DivisionThe Translational Genomics Research Institute (TGen)PhoenixUSA
  2. 2.Cancer Biology Graduate Interdisciplinary ProgramUniversity of ArizonaTucsonUSA
  3. 3.Center for Thoracic Disease and Transplantation, Heart and Lung InstituteSt. Joseph’s Hospital and Medical CenterPhoenixUSA
  4. 4.Integrated Cancer Genomics DivisionThe Translational Genomics Research Institute (TGen)PhoenixUSA
  5. 5.Diabetes, Cardiovascular and Metabolic Diseases DivisionThe Translational Genomics Research Institute (TGen)PhoenixUSA
  6. 6.Humboldt Medical SpecialistsEurekaUSA
  7. 7.Cancer Treatment Centers of AmericaGoodyearUSA