SERPINE2/PN-1 regulates the DNA damage response and radioresistance by activating ATM in lung cancer

doi:10.1016/j.canlet.2021.10.001

. 2022 Jan 1:524:268-283.

doi: 10.1016/j.canlet.2021.10.001. Epub 2021 Oct 11.

SERPINE2/PN-1 regulates the DNA damage response and radioresistance by activating ATM in lung cancer

Jingjing Zhang¹, Qiong Wu², Lucheng Zhu³, Shujun Xie¹, Linglan Tu⁴, Yuhong Yang⁵, Kan Wu³, Yanyan Zhao¹, Yuqing Wang¹, Yasi Xu¹, Xueqin Chen⁵, Shenglin Ma⁶, Shirong Zhang⁷

Affiliations

¹ Department of Translational Medicine Research Center, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Afﬁliated Hangzhou First People's Hospital, Zhejiang Chinese Medical University, Hangzhou, 310006, China; Department of Oncology, Afﬁliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Cancer Center, Zhejiang University, Hangzhou, 310006, China.
² Department of Translational Medicine Research Center, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Afﬁliated Hangzhou First People's Hospital, Zhejiang Chinese Medical University, Hangzhou, 310006, China.
³ Department of Oncology, Afﬁliated Hangzhou Cancer Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China.
⁴ Center for Molecular Medicine, Hangzhou Medical College, Hangzhou, 310013, China.
⁵ Department of Oncology, Afﬁliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Cancer Center, Zhejiang University, Hangzhou, 310006, China.
⁶ Department of Translational Medicine Research Center, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Afﬁliated Hangzhou First People's Hospital, Zhejiang Chinese Medical University, Hangzhou, 310006, China; Department of Oncology, Afﬁliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Cancer Center, Zhejiang University, Hangzhou, 310006, China; Department of Oncology, Afﬁliated Hangzhou Cancer Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China; Department of Cancer Medical Center, Affiliated Xiaoshan Hospital, Hangzhou Normal University, Hangzhou, 311201, China. Electronic address: mashenglin@medmail.com.cn.
⁷ Department of Translational Medicine Research Center, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Afﬁliated Hangzhou First People's Hospital, Zhejiang Chinese Medical University, Hangzhou, 310006, China; Department of Oncology, Afﬁliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Cancer Center, Zhejiang University, Hangzhou, 310006, China. Electronic address: shirleyz4444@zju.edu.cn.

PMID: 34648881
DOI: 10.1016/j.canlet.2021.10.001

Free article

SERPINE2/PN-1 regulates the DNA damage response and radioresistance by activating ATM in lung cancer

Jingjing Zhang et al. Cancer Lett. 2022.

Free article

. 2022 Jan 1:524:268-283.

doi: 10.1016/j.canlet.2021.10.001. Epub 2021 Oct 11.

Authors

Jingjing Zhang¹, Qiong Wu², Lucheng Zhu³, Shujun Xie¹, Linglan Tu⁴, Yuhong Yang⁵, Kan Wu³, Yanyan Zhao¹, Yuqing Wang¹, Yasi Xu¹, Xueqin Chen⁵, Shenglin Ma⁶, Shirong Zhang⁷

Affiliations

¹ Department of Translational Medicine Research Center, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Afﬁliated Hangzhou First People's Hospital, Zhejiang Chinese Medical University, Hangzhou, 310006, China; Department of Oncology, Afﬁliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Cancer Center, Zhejiang University, Hangzhou, 310006, China.
² Department of Translational Medicine Research Center, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Afﬁliated Hangzhou First People's Hospital, Zhejiang Chinese Medical University, Hangzhou, 310006, China.
³ Department of Oncology, Afﬁliated Hangzhou Cancer Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China.
⁴ Center for Molecular Medicine, Hangzhou Medical College, Hangzhou, 310013, China.
⁵ Department of Oncology, Afﬁliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Cancer Center, Zhejiang University, Hangzhou, 310006, China.
⁶ Department of Translational Medicine Research Center, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Afﬁliated Hangzhou First People's Hospital, Zhejiang Chinese Medical University, Hangzhou, 310006, China; Department of Oncology, Afﬁliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Cancer Center, Zhejiang University, Hangzhou, 310006, China; Department of Oncology, Afﬁliated Hangzhou Cancer Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China; Department of Cancer Medical Center, Affiliated Xiaoshan Hospital, Hangzhou Normal University, Hangzhou, 311201, China. Electronic address: mashenglin@medmail.com.cn.
⁷ Department of Translational Medicine Research Center, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Afﬁliated Hangzhou First People's Hospital, Zhejiang Chinese Medical University, Hangzhou, 310006, China; Department of Oncology, Afﬁliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Cancer Center, Zhejiang University, Hangzhou, 310006, China. Electronic address: shirleyz4444@zju.edu.cn.

PMID: 34648881
DOI: 10.1016/j.canlet.2021.10.001

Erratum in

Corrigendum to "SERPINE2/PN-1 regulates the DNA damage response and radioresistance by activating ATM in lung cancer" [Cancer Lett. 524 (2022) 268-283].
Zhang J, Wu Q, Zhu L, Xie S, Tu L, Yang Y, Wu K, Zhao Y, Wang Y, Xu Y, Chen X, Ma S, Zhang S. Zhang J, et al. Cancer Lett. 2025 Feb 1;610:217337. doi: 10.1016/j.canlet.2024.217337. Epub 2024 Nov 24. Cancer Lett. 2025. PMID: 39581824 No abstract available.

Abstract

Although the DNA damage response (DDR) is associated with the radioresistance characteristics of lung cancer cells, the specific regulators and underlying mechanisms of the DDR are unclear. Here, we identified the serine proteinase inhibitor clade E member 2 (SERPINE2) as a modulator of radiosensitivity and the DDR in lung cancer. Cells exhibiting radioresistance after ionizing radiation show upregulation of SERPINE2, and SERPINE2 knockdown improves tumor radiosensitivity in vitro and in vivo. Functionally, SERPINE2 deﬁciency causes a reduction in homologous recombination repair, rapid recovery of cell cycle checkpoints, and suppression of migration and invasion. Mechanistically, SERPINE2 knockdown inhibits the accumulation of p-ATM and the downstream repair protein RAD51 during DNA repair, and RAD51 can restore DNA damage and radioresistance phenotypes in lung cancer cells. Furthermore, SERPINE2 can directly interact with MRE11 and ATM to facilitate its phosphorylation in HR-mediated DSB repair. In addition, high SERPINE2 expression correlates with dismal prognosis in lung adenocarcinoma patients, and a high serum SERPINE2 concentration predicts a poor response to radiotherapy in non-small cell lung cancer patients. In summary, these ﬁndings indicate a novel regulatory mechanism by which SERPINE2 modulates the DDR and radioresistance in lung cancer.

Keywords: ATM; DNA damage response; Homologous recombination; SERPINE2; radioresistance.

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SERPINE2/PN-1 regulates the DNA damage response and radioresistance by activating ATM in lung cancer

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SERPINE2/PN-1 regulates the DNA damage response and radioresistance by activating ATM in lung cancer

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