title: P21-activated kinase 7 mediates cisplatin-resistance of esophageal squamous carcinoma cells with Aurora-A overexpression.
abstract: Aurora-A overexpression is common in various types of cancers and has been shown to be involved in tumorigenesis through different signaling pathways, yet how the deregulation affects cancer therapeutics remains elusive. Here we showed that overexpression of Aurora-A rendered esophageal cancer cells resistance to cisplatin (CDDP) by inhibiting apoptosis. By using an apoptosis array, we identified a downstream gene, p21-activated kinase 7 (PAK7). PAK7 was upregulated by Aurora-A overexpression at both mRNA and protein levels. Importantly, the expression levels of Aurora-A and PAK7 were correlated in ESCC primary samples. Chromatin immunoprecipitation (ChIP) assay revealed that binding of E2F1 to the promoter of PAK7 was significantly enhanced upon Aurora-A activation, and knockdown of transcription factor E2F1 decreased PAK7 expression, suggesting that Aurora-A regulated PAK7 through E2F1. Furthermore, we demonstrated that PAK7 knockdown led to increased apoptosis, and Aurora-A-induced resistance to CDDP was reversed by downregulation of PAK7, suggesting PAK7 was a downstream player of Aurora-A that mediated chemoresistance of ESCC cells to CDDP. Our data suggest that PAK7 may serve as an attractive candidate for therapeutics in ESCC patients with Aurora-A abnormality.
authors.affiliation: Laboratory of Cell and Molecular Biology and State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Shun
authors.initials: S
authors.lastname: He
authors.affiliation: Department of Pathology, West China Second University Hospital/West China Women's and Children's Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Feng
authors.affiliation: Laboratory of Cell and Molecular Biology and State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Mei
authors.initials: M
authors.lastname: Liu
authors.affiliation: Laboratory of Cell and Molecular Biology and State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Shangbin
authors.initials: S
authors.lastname: Yang
authors.affiliation: Laboratory of Cell and Molecular Biology and State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Yan
authors.affiliation: Laboratory of Cell and Molecular Biology and State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Laboratory of Cell and Molecular Biology and State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Zaozao
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Laboratory of Cell and Molecular Biology and State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Chenfei
authors.initials: C
authors.lastname: Hu
authors.affiliation: Laboratory of Cell and Molecular Biology and State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Laboratory of Cell and Molecular Biology and State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Lechuang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Laboratory of Cell and Molecular Biology and State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Laboratory of Cell and Molecular Biology and State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Ningzhi
authors.initials: N
authors.lastname: Xu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D064096:Aurora Kinase A / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D004947:Esophagus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D034622:RNA Interference; D015854:Up-Regulation; D054462:p21-Activated Kinases / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; C443802:PAK5 protein, human; D064096:Aurora Kinase A; D054462:p21-Activated Kinases; D002945:Cisplatin