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

Lingxue Xu; Jingjing Wang; Danhua Zhang; Lijie Song; Han Wu; Jianyao Wang; Jinxin Miao; Haoran Guo; Sujuan Fang; Lingling Si; Jingfei Chen; Yifan Wu; Yangyang Wu; Lihong Wang; Na Zhang; Louisa Chard; Yaohe Wang; Zhenguo Cheng

doi:10.1186/s13578-022-00802-w

Cell & Bioscience (May 2022)

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

Lingxue Xu,
Jingjing Wang,
Danhua Zhang,
Lijie Song,
Han Wu,
Jianyao Wang,
Jinxin Miao,
Haoran Guo,
Sujuan Fang,
Lingling Si,
Jingfei Chen,
Yifan Wu,
Yangyang Wu,
Lihong Wang,
Na Zhang,
Louisa Chard,
Yaohe Wang,
Zhenguo Cheng

Affiliations

Lingxue Xu: 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
Jingjing Wang: 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
Danhua Zhang: Department of Surgical Oncology, The First Affiliated Hospital of Zhengzhou University
Lijie Song: Department of Medical Oncology, The First Affiliated Hospital of Zhengzhou University
Han Wu: 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
Jianyao Wang: 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
Jinxin Miao: 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
Haoran Guo: 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
Sujuan Fang: 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
Lingling Si: 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
Jingfei Chen: 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
Yifan Wu: 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
Yangyang Wu: 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
Lihong Wang: 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
Na Zhang: 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
Louisa Chard: Centre for Biomarkers & Biotherapeutics, Barts Cancer Institute, Queen Mary University of London
Yaohe Wang: 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
Zhenguo Cheng: 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

DOI: https://doi.org/10.1186/s13578-022-00802-w
Journal volume & issue: Vol. 12, no. 1
pp. 1 – 14

Abstract

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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.

Published in Cell & Bioscience

ISSN: 2045-3701 (Online)
Publisher: BMC
Country of publisher: United Kingdom
LCC subjects: Technology: Chemical technology: Biotechnology; Science: Biology (General); Science: Chemistry: Organic chemistry: Biochemistry
Website: https://cellandbioscience.biomedcentral.com/

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