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 output: Contribution to journalArticle

14 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)613-623
Number of pages11
JournalClinical and Experimental Metastasis
Volume31
Issue number6
DOIs
StatePublished - Aug 2014

Keywords

  • FN14
  • MET
  • Metastasis
  • Non-small cell lung cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Whitsett, T. G., Fortin Ensign, S. P., Dhruv, H. D., Inge, L. J., Kurywchak, P., Wolf, K. K., LoBello, J., Kingsley, C. B., Allen, J. W., Weiss, G. J., & Tran, N. L. (2014). FN14 expression correlates with MET in NSCLC and promotes MET-driven cell invasion. Clinical and Experimental Metastasis, 31(6), 613-623. https://doi.org/10.1007/s10585-014-9653-6