2. Academic Validation
  3. The two-faced role of ATF2 on cisplatin response in gastric cancer depends on p53 context

The two-faced role of ATF2 on cisplatin response in gastric cancer depends on p53 context

  • Cell Biosci. 2022 May 31;12(1):77. doi: 10.1186/s13578-022-00802-w.
Lingxue Xu  # 1,  Jingjing Wang  # 1,  Danhua Zhang 2,  Lijie Song 3,  Han Wu 1 2,  Jianyao Wang 1,  Jinxin Miao 1,  Haoran Guo 1,  Sujuan Fang 1,  Lingling Si 1,  Jingfei Chen 1,  Yifan Wu 1,  Yangyang Wu 1,  Lihong Wang 1,  Na Zhang 1,  Louisa Chard 4,  Yaohe Wang 1 4,  Zhenguo Cheng 5
Affiliations

Affiliations

  • 1 National Center for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, State Key Laboratory of Esophageal Cancer Prevention and Treatment, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, 450052, Zhengzhou, China.
  • 2 Department of Surgical Oncology, The First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, China.
  • 3 Department of Medical Oncology, The First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, China.
  • 4 Centre for Biomarkers & Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, E1 4NS, London, United Kingdom.
  • 5 National Center for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, State Key Laboratory of Esophageal Cancer Prevention and Treatment, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, 450052, Zhengzhou, China. chengzhenguo@zzu.edu.cn.
  • # Contributed equally.
PMID: 35641966 DOI: 10.1186/s13578-022-00802-w
Abstract

Background: Activating transcription factor-2 (ATF2) is a member of the basic leucine zipper family of DNA-binding proteins, which exhibits both oncogenic and tumor suppression activity in different tumors. However, the molecular mechanism of its dual function in Cancer chemotherapy especially in gastric Cancer has still not been elucidated.

Methods: The protein expression and location of ATF2 in gastric Cancer tissues was detected with immunohistochemistry assay, and the clinical significance was analyzed using TCGA and GEO database. The activation and impact of ATF2 in cisplatin treated cells were evaluated with western blot, incucyte live Cell Analysis, clone formation and tumor xenografts assays. Interaction between ATF2 and p53 was confirmed with immunoprecipitation and GST-pull down. Potential molecular mechanism of ATF2 in different p53 status cells was analyzed with RNA sequencing and real-time quantitative PCR.

Results: ATF2 mainly located in the nucleus of Cancer cells, higher ATF2 level was associated with poor five-year survival of gastric patients, especially in those undergone chemotherapy treatment. Cisplatin treatment significantly activated ATF2 in p53 mutant cells. ATF2 could interact with the trans-activation domain of p53 and enhance cisplatin sensitivity in p53 wild type cell lines, while promoted cell survival in mutant p53 Cancer cells by affecting ERK1/2 pathway.

Conclusions: This study confirmed the effect of ATF2 on cisplatin sensitivity was associated with the functional status of p53 in gastric Cancer cells. Integrated analysis of ATF2 expression and P53 status could be used to evaluate the chemotherapy sensitivity and prognosis of gastric Cancer patients.

Keywords

ATF2; Cisplatin; ERK1/2; Gastric cancer; Prognosis; p53.

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