Epigenetic Downregulated ITGBL1 Promotes Non-small Cell Lung Cancer Cell Invasion Through Wnt/PCP Signaling

Integrin, beta-like 1 (ITGBL1), is a β-integrin-related extracellular matrix protein which contains ten EGF-like repeats domain. Surprisingly, we screen Oncomine Database and found that ITGBL1 is more commonly downregulated in non-small cell lung cancer (NSCLC) tissues, and the result reminds us to explore its significance in NSCLC. Thus, we retrieved DRUGSURV Database and found that downregulated ITGBL1 predicts a poor prognosis of patients. These results provided us the clues that ITGBL1 might be a tumor suppressor in NSCLC. However, the biological functions of ITGBL1 have not been reported to date. In the current study, we surprisingly found that knockdown of ITGBL1 in NSCLC cell lines could promote cancer cell migration and invasion. Furthermore, recombinant ITGBL1 protein-treated cancer cell could inhibit cell migration and invasion. These results suggested that ITGBL1 plays a suppressive role in NSCLC progression. We further found that the downregulation of ITGBL1 might result from highly expressed miR-576-5p in NSCLC tissues, and the activity of Wnt/PCP signaling was enhanced when the level of ITGBL1 was inhibited. In conclusion, our results suggest that ITGBL1 is a novel tumor suppressor in NSCLC progression.