Journal of Gastric Cancer

  • 제17권4호
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  • Pages.295-305
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  • 2017
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  • 2093-582X(pISSN)
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  • 2093-5641(eISSN)
대한위암학회 (The Korean Gastric Cancer Association)
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ATM Signaling Pathway Is Implicated in the SMYD3-mediated Proliferation and Migration of Gastric Cancer Cells

  • Wang, Lei (Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin University of Science and Technology) ;
  • Wang, Qiu-Tong (Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin University of Science and Technology) ;
  • Liu, Yu-Peng (Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin University of Science and Technology) ;
  • Dong, Qing-Qing (Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin University of Science and Technology) ;
  • Hu, Hai-Jie (Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin University of Science and Technology) ;
  • Miao, Zhi (Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin University of Science and Technology) ;
  • Li, Shuang (Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin University of Science and Technology) ;
  • Liu, Yong (Department of Gastric Cancer Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer) ;
  • Zhou, Hao (Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin University of Science and Technology) ;
  • Zhang, Tong-Cun (Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin University of Science and Technology) ;
  • Ma, Wen-Jian (Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin University of Science and Technology) ;
  • Luo, Xue-Gang (Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin University of Science and Technology)
  • 투고 : 2017.08.03
  • 심사 : 2017.10.16
  • 발행 : 2017.12.31
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초록

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.

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참고문헌

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  2. SMYD3 promoter hypomethylation is associated with the risk of colorectal cancer vol.14, pp.18, 2017, https://doi.org/10.2217/fon-2017-0682
  3. Small-molecule inhibitors of lysine methyltransferases SMYD2 and SMYD3: current trends vol.11, pp.8, 2017, https://doi.org/10.4155/fmc-2018-0380
  4. Amplification of SMYD3 promotes tumorigenicity and intrahepatic metastasis of hepatocellular carcinoma via upregulation of CDK2 and MMP2 vol.38, pp.25, 2017, https://doi.org/10.1038/s41388-019-0766-x
  5. Cannabidiol Induces Cell Cycle Arrest and Cell Apoptosis in Human Gastric Cancer SGC-7901 Cells vol.9, pp.8, 2017, https://doi.org/10.3390/biom9080302
  6. SMYD2 promotes cervical cancer growth by stimulating cell proliferation vol.9, pp.1, 2019, https://doi.org/10.1186/s13578-019-0340-9
  7. SMYD3: An Oncogenic Driver Targeting Epigenetic Regulation and Signaling Pathways vol.12, pp.1, 2017, https://doi.org/10.3390/cancers12010142
  8. Targeting SMYD3 to Sensitize Homologous Recombination-Proficient Tumors to PARP-Mediated Synthetic Lethality vol.23, pp.10, 2017, https://doi.org/10.1016/j.isci.2020.101604
  9. SMYD3 promotes hepatocellular carcinoma progression by methylating S1PR1 promoters vol.12, pp.8, 2017, https://doi.org/10.1038/s41419-021-04009-8
  10. Playing on the Dark Side: SMYD3 Acts as a Cancer Genome Keeper in Gastrointestinal Malignancies vol.13, pp.17, 2017, https://doi.org/10.3390/cancers13174427
  11. SMYD3: a regulator of epigenetic and signaling pathways in cancer vol.13, pp.1, 2017, https://doi.org/10.1186/s13148-021-01021-9
  12. SMYD3: a regulator of epigenetic and signaling pathways in cancer vol.13, pp.1, 2017, https://doi.org/10.1186/s13148-021-01021-9