title: PAK1-mediated MORC2 phosphorylation promotes gastric tumorigenesis.
abstract: To date, microrchidia (MORC) family CW-type zinc-finger 2 (MORC2), has been found to be involved in p21-activated kinase1 (PAK1) pathway to maintain genomic integrity. Here, we explore its novel role in cancer. We demonstrate that PAK1-mediated MORC2 phosphorylation promotes cell cycle progression, defective phosphorylation of MORC2-S677A results in attenuated cell proliferation and tumorigenicity of gastric cancer cells, which is significantly enhanced in overexpression of phospho-mimic MORC2-S677E form, suggesting the importance of MORC2 phosphorylation in tumorigenesis. More importantly, phosphorylation of MORC2 correlates positively with PAK1 expression in clinical gastric cancer. Furthermore, high expression of PAK1 and phosphorylation of MORC2 appear to be associated with poor prognosis of clinical gastric cancer. Collectively, these findings revealed a novel function of MORC2 phosphorylation in promoting gastric cell proliferation in vitro and tumorigenesis in vivo, suggesting that blocking PAK1-mediated MORC2 phosphorylation might be a potential therapeutic strategy for gastric tumorigenesis.
authors.affiliation: Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.
authors.forename: Guiling
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.
authors.forename: Furong
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.
authors.forename: Xinze
authors.initials: X
authors.lastname: Cai
authors.affiliation: Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, Shenyang, China.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Miao
authors.affiliation: Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.
authors.forename: Hongde
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, Shenyang, China.
authors.forename: Huimian
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Cao
authors.affiliation: Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
mesh_terms: D000818:Animals; D063646:Carcinogenesis; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000378:metabolism; D012694:Serine / Q000737:chemistry; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000628:therapy; D014157:Transcription Factors / Q000378:metabolism*; D016896:Treatment Outcome; D054462:p21-Activated Kinases / Q000378:metabolism*
chemical_list: C549896:MORC2 protein, human; C586981:MORC2 protein, mouse; D034741:RNA, Small Interfering; D014157:Transcription Factors; D012694:Serine; C515903:PAK1 protein, human; C515905:Pak1 protein, mouse; D054462:p21-Activated Kinases
keywords: MORC2; P21-activated kinase 1(PAK1); gastric cancer; phosphorylation