Arizona Health Sciences

Fn14 receptor promotes invasive potential and metastatic capacity of non-small lung adenocarcinoma cells through the up-regulation of integrin α6.

TitleFn14 receptor promotes invasive potential and metastatic capacity of non-small lung adenocarcinoma cells through the up-regulation of integrin α6.
Publication TypeJournal Article
Year of Publication2015
AuthorsJandova J, Mason CJ, Pawar SC, Watts GS
JournalNeoplasma
Volume62
Issue1
Pagination41-52
Date Published2015
ISSN0028-2685
Abstract

UNLABELLED: Lung cancer is one of the leading cause of cancer-related death around the world with the majority of diagnoses being non-small cell lung cancer (NSCLC). Given the poor survival rate and efficacy of current therapy for NSCLC, there is a need to identify and develop new therapeutic targets for treatment. We have observed significantly up-regulated levels of Fn14 in clinical samples of lung cancer relative to normal adjacent tissue. However, the functional role of Fn14 in these tumors is not understood yet. We used RT-PCR to establish the Fn14 expression profile in various NSCLC cell lines. Using isogenic variants of H460 NSCLC cell line with low, intermediate and high Fn14 expression as a cellular model, we determined that increased levels of integrin α6 in cells over-expressing Fn14 is suggestive of an important role of α6β1-fn14 interactions in motility of lung carcinoma and formation of metastases. Enhanced levels of Fn14 correlated with higher tumor cell migration and invasion in an MMP-1 dependent manner. Cells over-expressing Fn14 showed increased in vivo tumor formation with metastatic capacity to lymph nodes, lungs and liver. Thus, this research may be a step toward developing improved treatment strategies for NSCLC by improved detection and inhibition of metastases.

KEYWORDS: Fn14, TNFRSF12A, non-small cell lung cancer, H460 cells, motility, tumor formation and metastasis, integrin α6.

Alternate JournalNeoplasma
PubMed ID25563366
PubMed Central IDPMC4455767
Grant ListP30 CA023074 / CA / NCI NIH HHS / United States
P30 ES006694 / ES / NIEHS NIH HHS / United States
Faculty Member Reference: 
George Watts, Ph.D.