title: PAK4 confers the malignance of cervical cancers and contributes to the cisplatin-resistance in cervical cancer cells via PI3K/AKT pathway.
abstract: BACKGROUND
  Multiple protein or microRNA markers have been recognized to contribute to the progression and recurrence of cervical cancers. Particular those, which are associated with the chemo- or radio-resistance of cervical cancers, have been proposed to be promising and to facilitate the definition for cervical cancer treatment options.
  
  
  METHODS
  This study was designed to explore the potential prognosis value of p21-activated kinase (PAK)-4 in cervical cancer, via the Kaplan-Meier analysis, log-rank test and Cox regression analysis, and then to investigate the regulatory role of PAK4 in the cisplatin resistance in cervical cancer cells, via the strategies of both PAK4 overexpression and PAK4 knockout.
  
  
  RESULTS
  It was demonstrated that PAK4 was upregulated in cervical cancer tissues, in an association with the cancer's malignance variables such as FIGO stage, lymph node or distant metastasis and the poor histological grade. The high PAK4 expression was also independently associated with poor prognosis to cervical cancer patients. Moreover, PAK4 confers cisplatin resistance in cervical cancer Hela or Caski cells. In addition, the PI3K/Akt pathway has been implicated in the PAK4-confered cisplatin resistance. And the PI3K/Akt inhibitor, LY294002, markedly deteriorated the cisplatin-mediated viability reduction of Hela or Caski cells, indicating the involvement of PI3K/Akt pathway in the cisplatin resistance in cervical cancer cells.
  
  
  CONCLUSIONS
  This study has confirmed the significant prognostic role of PAK4 level in cervical cancer patients and has recognized the regulatory role in cervical cancer progression. Moreover, our study has indicated that PAK4 also confers the chemoresistance of cervical cancer cells in a PI3K/Akt-dependent way. Thus, our study indicates PAK4 as a promising marker for cervical cancer treatment.
authors.affiliation: School of Pharmaceutical Science and Technology, Tianjin University, No. 92, Weijin Road, Nankai District, Tianjin, 300072, China.|Tianjin Huanhu Hospital, No.122, Qixiangtai Road, Hexi District, Tianjin, 300060, China.
authors.forename: Xiang-Rong
authors.initials: XR
authors.lastname: Shu
authors.affiliation: School of Pharmaceutical Science and Technology, Tianjin University, No. 92, Weijin Road, Nankai District, Tianjin, 300072, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: School of Pharmaceutical Science and Technology, Tianjin University, No. 92, Weijin Road, Nankai District, Tianjin, 300072, China. hsunyt2013@163.com.
authors.forename: He
authors.initials: H
authors.lastname: Sun
authors.affiliation: Haidian Maternal & Child Health Hospital, Beijing, 10080, China.
authors.forename: Li-Qun
authors.initials: LQ
authors.lastname: Chi
authors.affiliation: Tianjin Huanhu Hospital, No.122, Qixiangtai Road, Hexi District, Tianjin, 300060, China. gringwang@163.com.
authors.forename: Jin-Huan
authors.initials: JH
authors.lastname: Wang
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000235:genetics / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D002945:Cisplatin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005260:Female; D006367:HeLa Cells; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D034622:RNA Interference; D012307:Risk Factors; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection; D002583:Uterine Cervical Neoplasms / Q000201:enzymology / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D054462:p21-Activated Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; C116367:PAK4 protein, human; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D054462:p21-Activated Kinases; D002945:Cisplatin