title: PAK6 increase chemoresistance and is a prognostic marker for stage II and III colon cancer patients undergoing 5-FU based chemotherapy.
abstract: p21-Activated kinase 6 (PAK6) has been implicated in radiotherapy and docetaxel resistance. We have further evaluated PAK6 as a predictor of 5-fluorouracil (5-FU) treatment response in colon cancer. Here we report that in colon cancer PAK6 promotes tumor progression and chemoresistance both in vitro and in vivo. In the clinical analysis, PAK6 was overexpressed in 104 of 147 (70.75%) stage II and III patients who received 5-FU based chemotherapy after surgery. Multivariate Cox regression analysis indicated that PAK6 was an independent prognostic factor for overall survival (P < 0.001) and disease-free survival (P < 0.001). Colon cancer cell lines showed increased PAK6 expression upon 5-FU treatment. In PAK6-knockdown cells treated with 5-FU, cell viability and phosphorylation of BAD decreased, and the number of apoptotic cells, levels of cleaved caspase 3 and PARP increased compared to control cells. The opposite was observed in PAK6 overexpressing cells. Short hairpin RNA knockdown of PAK6 blocked cells in G2-M phase. Furthermore, Animal experiments results in vivo are consistent with outcomes in vitro. This study demonstrates that PAK6 is an independent prognostic factor for adjuvant 5-FU-based chemotherapy in patients with stage II and stage III colon cancer.
authors.affiliation: Department of General Surgery, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Pathology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Huijun
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of General Surgery, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Dongwang
authors.initials: D
authors.lastname: Yan
authors.affiliation: Department of General Surgery, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Cui
authors.affiliation: Department of General Surgery, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Fudong
authors.initials: F
authors.lastname: Yu
authors.affiliation: Department of General Surgery, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Yingming
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Basic Medical College, Taishan Medical University, Tai'an, People's Republic of China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Feng
authors.affiliation: Department of General Surgery, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Jingtao
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Anal-Colorectal Surgery, General Hospital of Ningxia Medical University, Yinchuan, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Department of Pathology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Senlin
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of General Surgery, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Pathology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Huamei
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of General Surgery, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Zhihai
authors.initials: Z
authors.lastname: Peng
mesh_terms: D000368:Aged; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011379:Prognosis; D016016:Proportional Hazards Models; D014162:Transfection; D054462:p21-Activated Kinases / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C429007:PAK6 protein, human; D054462:p21-Activated Kinases; D005472:Fluorouracil