DRAK1 Promotes Migration And Invasion Of Non-small-cell Lung Cancer Via TGF-? / Smad Signaling

Objective: DRAK1 also named serine / threonine kinase 17A(STK17A)was a ubiquitously expressed kinase.DRAK1 was originally identified as a regulator of apoptosis.Its expression and biological function in malignant tumors are limited,and its role in non-small-cell lung cancer has not yet to be confirmed.This article aims to investigate the expression and biological function of DRAK1 in NSCLCand preliminary to explore the relevant molecular mechanisms.Methods: 1.IHC was used to determine the expression and localization of DRAK1 in NSCLC tissues and adjacent tissues,and we analyse the relationship between DRAK1 expression and clinicopathological factors as well as the relationship with clinical prognosis 2.Immunoblotting was used to investigate the expression of DRAK1 in fresh tissues of NSCLCand paired normal adjacent tissues.3.Immunoblotting and immunofluorescence were used to detected expression and localization of DRAK1 in lung cancer cell lines 4.To study the influence of DRAK1 on the migration and invasion of lung cancer cells through cell scratch experiments and matrigel invasion experiments5.The expression of DRAK1 was up-regulatedand down-regulated respectively in A549 and LK2 cells to studythe expression changes ofinvasion and EMT-related proteins.6.Immunofluorescence and Coimmunoprecipitation were used to determine the protein co-localized and bound to DRAK1.Results:1.DRAK1 was mainly overexpressed in the NSCLC tissues cytoplasm,its expression was significantlyhigher than normal lung tissues which adjacent to the cancer.Overexpressed DRAK1 in the cytoplasm was relevant to advanced TNM stage and distance lymph node metastasis.DRAK1 Overexpression had a correlation with poor prognosis.Western blot results showed that DRAK1 protein expression in lung cancer tissue was significantly higher than that in normal lung tissue paired to the cancertissue.The cell line results showed that: DRAK1 expression in LK2? PC9? A549 ? H460 ?H661 lung cancer cell lines was significantly higher than that in HBE? H1299?SK cell lines.2.In A549 cell line,overexpression of DRAK1 can promote cell migration and invasion.Knockdown of DRAK1 protein expression in LK2 cell line can inhibit cell migration and invasion.4.Treating with TGF-? / Smad pathway inhibitor can reverse the effect of DRAK1 on lung cancer cell migration ? invasion and EMT process.5.DRAK1 can bind to Smad3.Conclusion:1.DRAK1 is abnormally expressed in NSCLCand related to poor clinical outcomes.DRAK1 promotes the migration,invasion and EMT of NSCLC cells possibly via TGF-? / Smad signaling.