title: A role for p21-activated kinase 7 in the development of gastric cancer.
abstract: p21-activated kinase (PAK)7 (also known as PAK5) is a member of the group B PAK family of serine/threonine protein kinases, which are effectors of the small GTPases Rac and CDC42. PAK7 can promote neurite outgrowth, induce microtubule stabilization, and activate cell survival signaling pathways. However, the role of PAK7 in cancer is still poorly understood. Here, we showed that PAK7 expression was upregulated in different gastric cancer cell lines and gastric cancer tissues, as compared with human embryonic kidney 293 cells and adjacent normal tissues, respectively. The results suggested that PAK7 expression was related to gastric cancer progression. Thus, we employed lentivirus-mediated small interfering RNA to inhibit PAK7 expression, to investigate the role of PAK7 in human gastric carcinogenesis. RNA interference efficiently downregulated expression of PAK7 in SGC-7901 and MGC-803 cells at both mRNA and protein levels. Knockdown of PAK7 inhibited human gastric cancer cell proliferation by inducing cell cycle arrest in G(0)/G(1) phase, in concordance with the downregulation of CDK2, CDC25A, and cyclin D1. Our data suggest that PAK7 is a new hallmark of gastric cancer, in which PAK7 might contribute to gain of tumor growth potential, acting by affecting the expression of cell cycle regulators. Therefore, PAK7 may be an attractive candidate as a therapeutic target in gastric cancer.
authors.affiliation: Department of General Surgery, Xinhua Hospital, Affiliated to School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Gu
authors.forename: Keqiang
authors.initials: K
authors.lastname: Li
authors.forename: Maolan
authors.initials: M
authors.lastname: Li
authors.forename: Xiangsong
authors.initials: X
authors.lastname: Wu
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Qichen
authors.initials: Q
authors.lastname: Ding
authors.forename: Wenguang
authors.initials: W
authors.lastname: Wu
authors.forename: Jiahua
authors.initials: J
authors.lastname: Yang
authors.forename: Jiasheng
authors.initials: J
authors.lastname: Mu
authors.forename: Hao
authors.initials: H
authors.lastname: Wen
authors.forename: Qian
authors.initials: Q
authors.lastname: Ding
authors.forename: Jianhua
authors.initials: J
authors.lastname: Lu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Hao
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Wenjie
authors.initials: W
authors.lastname: Zhang
authors.forename: Songgang
authors.initials: S
authors.lastname: Li
authors.forename: Yingbin
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics / Q000378:metabolism; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D008875:Middle Aged; D034622:RNA Interference; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000473:pathology; D020687:cdc25 Phosphatases / Q000235:genetics / Q000378:metabolism; D054462:p21-Activated Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: C530104:CCND1 protein, human; D019938:Cyclin D1; C443802:PAK5 protein, human; D054462:p21-Activated Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; C517004:CDC25A protein, human; D020687:cdc25 Phosphatases