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

Abstract

Lung cancer is one of the leading causes 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.

Genetic Target Modulation Employing CRISPR/Cas9 Identifies Glyoxalase 1 as a Novel Molecular Determinant of Invasion and Metastasis in A375 Human Malignant Melanoma Cells In Vitro and In Vivo

“…Following a published standard procedure, pre-warmed Matrigel (37 °C; 300 μL) was added to each well of a 24-well plate followed by solidification (2 h) in the biosafety cabinet [ 48 ]. Cells (20 × 10 4 ; resuspended in 1 mL of normal growth medium) were then placed on top and incubated (37 °C, 5%CO 2 ).…”

Integrin α6 promotes esophageal cancer metastasis and is targeted by miR-92b

“…Integrin α6 stimulates metastasis of breast cancer, colorectal cancer, prostate cancer, and non-small lung adenocarcinoma [12–15]. Data presented here demonstrate a strong association between the increased expression of integrin α6 and the lymph node metastasis of ESCC.…”

miR-149-5p inhibits cell growth by regulating TWEAK/Fn14/PI3K/AKT pathway and predicts favorable survival in human osteosarcoma

“… 33 , 34 High expression of TWEAK/Fn14, related with EGFR activation, promotes tumor invasion and metastasis. 35 – 37 TWEAK–Fn14 interaction contributes to cell growth, angiogenesis, and drug resistance in gastric cancer. 38 Activation of the TWEAK–Fn14 axis leads to the activation of the PI3K/AKT signaling pathway, thus promoting the tumorigenesis.…”