title: Overexpression of P21-activated kinase 4 is associated with poor prognosis in non-small cell lung cancer and promotes migration and invasion.
abstract: BACKGROUND
  P21-activated kinase 4 (PAK4), an effector of the Rho family protein Cdc42, is an important oncogene whose expression is increased in many human cancers and is generally positively correlated with advanced disease and decreased survival. However, little is known about the expression and biological function of PAK4 in human non-small cell lung cancer (NSCLC).
  
  
  METHODS
  PAK4 expression in NSCLC tissues and adjacent non-tumor tissues were assessed by immunohistochemistry, real-time PCR, and western blotting. Prognostic value of PAK4 expression was evaluated by Kaplan-Meier analysis and Cox regression. siRNA-mediated gene silencing and protein kinase assay was applied to demonstrate the role and the mechanism of PAK4 in lung cancer cell migration, invasion.
  
  
  RESULTS
  The results showed that PAK4 was overexpressed in NSCLC cell lines and human NSCLC tissues. PAK4 expression was detected both in the membranes and cytoplasm of NSCLC cancer cells in vivo. Moreover, increased expression of PAK4 was associated with metastasis, shorter overall survival, advanced stage of NSCLC. Furthermore, PAK4 expression was positively correlated with phosphorylation of LIMK1 expression levels. Knockdown of PAK4 in NSCLC cell lines led to reduce the phosphorylation of LIMK1, which resulted in decrease of the cell migration and invasion. In addition, PAK4 bound to LIMK1 directly and activated it via phosphorylation.
  
  
  CONCLUSIONS
  These data demonstrate that PAK4 mediated LIMK1 phosphorylation regulates the migration and invasion in NSCLC. Therefore, PAK4 might be a significant prognostic marker and potential therapeutic molecular target in NSCLC.
authors.affiliation: Department of Cardiothoracic Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. songwangcai@yahoo.com.
authors.forename: Songwang
authors.initials: S
authors.lastname: Cai
authors.affiliation: Department of Emergency, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. zqye@163.com.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Ye
authors.affiliation: Department of Radiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. wxhcrz@163.com.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pathylogy, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. p.yuhang@163.com.
authors.forename: Yuhang
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Department of Cardiothoracic Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. 573563237@qq.com.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Weng
authors.affiliation: Department of Cardiothoracic Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. laox222@126.com.
authors.forename: Sen
authors.initials: S
authors.lastname: Lao
authors.affiliation: Department of Gastrointestinal Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. drweihb@126.com.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Biocontrol, Sun Yat-sen (Zhongshan) University, Guangzhou, Guangdong, China. lilian-75@163.com.
authors.forename: Lian
authors.initials: L
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D054461:Lim Kinases / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D011379:Prognosis; D034741:RNA, Small Interfering / Q000235:genetics; D054462:p21-Activated Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; C116367:PAK4 protein, human; C515892:LIMK1 protein, human; D054461:Lim Kinases; D054462:p21-Activated Kinases