ATM Signaling Pathway Is Implicated in the SMYD3-mediated Proliferation and Migration of Gastric Cancer Cells

Lei Wang; Qiu-Tong Wang; Yu-Peng Liu; Qing-Qing Dong; Hai-Jie Hu; Zhi Miao; Shuang Li; Yong Liu; Hao Zhou; Tong-Cun Zhang; Wen-Jian Ma; Xuegang Luo

doi:https://doi.org/10.5230/jgc.2017.17.e33

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자료유형: 학술저널

저자정보: Lei Wang (Tianjin University of Science and Technology Tianjin China) Qiu-Tong Wang (Tianjin University of Science and Technology Tianjin China) Yu-Peng Liu (Tianjin University of Science and Technology) Qing-Qing Dong (Tianjin University of Science and Technology) Hai-Jie Hu (Tianjin University of Science and Technology) Zhi Miao (Tianjin University of Science and Technology) Shuang Li (Tianjin University of Science and Technology) Yong Liu (Tianjin Medical University Cancer Institute and Hospital) Hao Zhou (Tianjin University of Science and Technology) Tong-Cun Zhang (Tianjin University of Science and Technology) Wen-Jian Ma (Tianjin University of Science and Technology) Xuegang Luo (Tianjin University of Science and Technology)

저널정보: 대한위암학회 Journal of Gastric Cancer Journal of Gastric Cancer 제17권 제4호

발행연도: 2017.12

수록면: 295 - 305 (11page)

DOI: https://doi.org/10.5230/jgc.2017.17.e33

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Purpose: We previously found that the histone methyltransferase suppressor of variegation, enhancer of zeste, trithorax and myeloid-nervy-deformed epidermal autoregulatory factor-1 domain-containing protein 3 (SMYD3) is a potential independent predictive factor or prognostic factor for overall survival in gastric cancer patients, but its roles seem to differ from those in other cancers. Therefore, in this study, the detailed functions of SMYD3 in cell proliferation and migration in gastric cancer were examined. Materials and Methods: SMYD3 was overexpressed or suppressed by transfection with an expression plasmid or siRNA, and a wound healing migration assay and Transwell assay were performed to detect the migration and invasion ability of gastric cancer cells. Additionally, an MTT assay and clonogenic assay were performed to evaluate cell proliferation, and a cell cycle analysis was performed by propidium iodide staining. Furthermore, the expression of genes implicated in the ataxia telangiectasia mutated (ATM) pathway and proteins involved in cell cycle regulation were detected by polymerase chain reaction and western blot analyses. Results: Compared with control cells, gastric cancer cells transfected with si-SMYD3 showed lower migration and invasion abilities (P<0.05), and the absence of SMYD3 halted cells in G2/M phase and activated the ATM pathway. Furthermore, the opposite patterns were observed when SMYD3 was elevated in normal gastric cells. Conclusions: To the best of our knowledge, this study provides the first evidence that the absence of SMYD3 could inhibit the migration, invasion, and proliferation of gastric cancer cells and halt cells in G2/M phase via the ATM-CHK2/p53-Cdc25C pathway. These findings indicated that SMYD3 plays crucial roles in the proliferation, migration, and invasion of gastric cancer cells and may be a useful therapeutic target in human gastric carcinomas.

#SMYD3 protein #human #Stomach neoplasms #G2 phase cell cycle checkpoints #ATM pathway

참고문헌 (2)

참고문헌 신청

Shu-zhen Wang / 2008 / Knockdown of SMYD3 by RNA interference inhibits cervicalcarcinoma cell growth and invasion in vitro / BMB reports 41(4):294~299

Ren TN / 2011 / Effects of SMYD3 over-expression on cell cycle acceleration and cell proliferation in MDA-MB-231 human breast cancer cells / Med Oncol 28(Suppl 1):S91~S98

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