{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T09:27:03Z","timestamp":1740130023218,"version":"3.37.3"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2021,1,8]],"date-time":"2021-01-08T00:00:00Z","timestamp":1610064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31771580","81702795"],"award-info":[{"award-number":["31771580","81702795"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Sichuan Science and Technology Program","award":["2017FZ0034","2019JDTD0020","2020YFH0019"],"award-info":[{"award-number":["2017FZ0034","2019JDTD0020","2020YFH0019"]}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["2018NZD17","SCU2019C4198"],"award-info":[{"award-number":["2018NZD17","SCU2019C4198"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,4,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Impairment of genome instability drives the development of cancer by disrupting anti-cancer barriers. Upon genotoxic insults, DNA damage responsive factors, notably ATM kinase, is crucial to protect genomic integrity while promoting cell death. Meanwhile, cytotoxic therapy-inducing DNA lesions is double-edged sword by causing cancer metastasis based on animal models and clinical observations. The underlying mechanisms for the procancer effect of cytotoxic therapies are poorly understood. Here, we report that cancer cells subjected to cytotoxic treatments elicit dramatic alteration of gene expression controlling the potential of epithelium-mesenchyme transition (EMT). Resultantly, EMT-dependent cell mobility is potently induced upon DNA damage. This stimulation of EMT is mainly Ataxia-Telangiectasia-mutated (ATM)-dependent, as the chemical inhibitor specifically inhibiting ATM kinase activity can suppress the EMT gene expression and thus cell mobility. At last, we show that cancer cells with ATM activation display increased metastatic potential in ovarian cancer tissues. Taken together, we reveal a novel role of ATM in promoting metastatic potential of cancer cells by favoring EMT gene expression.<\/jats:p>","DOI":"10.1093\/carcin\/bgab002","type":"journal-article","created":{"date-parts":[[2021,1,8]],"date-time":"2021-01-08T19:09:55Z","timestamp":1610132995000},"page":"640-649","source":"Crossref","is-referenced-by-count":1,"title":["Implication of Ataxia-Telangiectasia-mutated kinase in epithelium-mesenchyme transition"],"prefix":"10.1093","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5192-6784","authenticated-orcid":false,"given":"Tianyu","family":"Miao","sequence":"first","affiliation":[{"name":"Vascular Surgery of West China Hospital, Sichuan University, Chengdu, PR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changsheng","family":"Peng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Ministry of Education), Department of Gynecology, West China Second University Hospital, Sichuan University, Chengdu, PR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zizhi","family":"Tang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Ministry of Education), Department of Gynecology, West China Second University Hospital, Sichuan University, Chengdu, PR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming","family":"Zeng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Ministry of Education), Department of Gynecology, West China Second University Hospital, Sichuan University, Chengdu, PR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shi","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Ministry of Education), Department of Gynecology, West China Second University Hospital, Sichuan University, Chengdu, PR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaojun","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Ministry of Education), Department of Gynecology, West China Second University Hospital, Sichuan University, Chengdu, PR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liandi","family":"Guo","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Southwest Minzu University, Chengdu, PR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaobo","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Ministry of Education), Department of Gynecology, West China Second University Hospital, Sichuan University, Chengdu, PR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jichun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Vascular Surgery of West China Hospital, Sichuan University, Chengdu, PR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingcai","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Suining Central Hospital, Suining, PR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Ministry of Education), Department of Gynecology, West China Second University Hospital, Sichuan University, Chengdu, PR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cong","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Ministry of Education), Department of Gynecology, West China Second University Hospital, Sichuan University, Chengdu, PR China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,1,8]]},"reference":[{"key":"2021043015503671900_CIT0001","doi-asserted-by":"crossref","first-page":"eaan0026","DOI":"10.1126\/scitranslmed.aan0026","article-title":"Neoadjuvant chemotherapy induces breast cancer metastasis through a TMEM-mediated mechanism","volume":"9","author":"Karagiannis","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"2021043015503671900_CIT0002","doi-asserted-by":"crossref","first-page":"E7159","DOI":"10.1073\/pnas.1700455114","article-title":"Stress-inducible gene Atf3 in the noncancer host cells contributes to chemotherapy-exacerbated breast cancer metastasis","volume":"114","author":"Chang","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA.,"},{"key":"2021043015503671900_CIT0003","doi-asserted-by":"crossref","first-page":"110733","DOI":"10.18632\/oncotarget.22717","article-title":"Chemotherapy-induced metastasis in breast cancer","volume":"8","author":"Karagiannis","year":"2017","journal-title":"Oncotarget,"},{"key":"2021043015503671900_CIT0004","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.cell.2009.11.007","article-title":"Epithelial-mesenchymal transitions in development and disease","volume":"139","author":"Thiery","year":"2009","journal-title":"Cell,"},{"key":"2021043015503671900_CIT0005","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1016\/j.cell.2008.03.027","article-title":"The epithelial-mesenchymal transition generates cells with properties of stem cells","volume":"133","author":"Mani","year":"2008","journal-title":"Cell,"},{"key":"2021043015503671900_CIT0006","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s40169-015-0048-3","article-title":"EMT and tumor metastasis","volume":"4","author":"Heerboth","year":"2015","journal-title":"Clin. Transl. Med.,"},{"key":"2021043015503671900_CIT0007","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.yexmp.2010.05.008","article-title":"SNAIL induces epithelial-to-mesenchymal transition in a human pancreatic cancer cell line (BxPC3) and promotes distant metastasis and invasiveness in vivo","volume":"89","author":"Nishioka","year":"2010","journal-title":"Exp. Mol. Pathol."},{"key":"2021043015503671900_CIT0008","doi-asserted-by":"crossref","first-page":"379","DOI":"10.4161\/cbt.23761","article-title":"Chemotherapy induced DNA damage response: convergence of drugs and pathways","volume":"14","author":"Woods","year":"2013","journal-title":"Cancer Biol. Ther.,"},{"key":"2021043015503671900_CIT0009","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/j.molcel.2017.05.015","article-title":"ATM, ATR, and DNA-PK: the trinity at the heart of the DNA damage response","volume":"66","author":"Blackford","year":"2017","journal-title":"Mol. Cell,"},{"key":"2021043015503671900_CIT0010","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1038\/3207","article-title":"ATM: the p53 booster","volume":"4","author":"Nakamura","year":"1998","journal-title":"Nat. Med.,"},{"key":"2021043015503671900_CIT0011","doi-asserted-by":"crossref","first-page":"12491","DOI":"10.1074\/jbc.C200093200","article-title":"ATM mediates phosphorylation at multiple p53 sites, including Ser(46), in response to ionizing radiation","volume":"277","author":"Saito","year":"2002","journal-title":"J. Biol. Chem.,"},{"key":"2021043015503671900_CIT0012","doi-asserted-by":"crossref","first-page":"195","DOI":"10.3858\/emm.2010.42.3.020","article-title":"ATM modulates transcription in response to histone deacetylase inhibition as part of its DNA damage response","volume":"42","author":"Jang","year":"2010","journal-title":"Exp. Mol. Med.,"},{"key":"2021043015503671900_CIT0013","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1080\/19491034.2016.1177681","article-title":"Collaboration of MLLT1\/ENL, Polycomb and ATM for transcription and genome integrity","volume":"7","author":"Ui","year":"2016","journal-title":"Nucleus,"},{"key":"2021043015503671900_CIT0014","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1158\/0008-5472.CAN-19-2255","article-title":"ATM paradoxically promotes oncogenic transformation via transcriptional reprogramming","volume":"80","author":"Liu","year":"2020","journal-title":"Cancer Res.,"},{"key":"2021043015503671900_CIT0015","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1093\/jmcb\/mjs048","article-title":"Activation of the ATM-Snail pathway promotes breast cancer metastasis","volume":"4","author":"Sun","year":"2012","journal-title":"J. Mol. Cell Biol.,"},{"key":"2021043015503671900_CIT0016","first-page":"7045","article-title":"ATM\u2011JAK\u2011PD\u2011L1 signaling pathway inhibition decreases EMT and metastasis of androgen\u2011independent prostate cancer","volume":"17","author":"Zhang","year":"2018","journal-title":"Mol. Med. Rep.,"},{"key":"2021043015503671900_CIT0017","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1128\/MCB.21.1.281-288.2001","article-title":"DNA damage-dependent nuclear dynamics of the Mre11 complex","volume":"21","author":"Mirzoeva","year":"2001","journal-title":"Mol. Cell. Biol.,"},{"key":"2021043015503671900_CIT0018","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.ygyno.2014.03.556","article-title":"Overexpression of long non-coding RNA HOTAIR predicts poor patient prognosis and promotes tumor metastasis in epithelial ovarian cancer","volume":"134","author":"Qiu","year":"2014","journal-title":"Gynecol. Oncol.,"},{"key":"2021043015503671900_CIT0019","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.1038\/sj.bjc.6600326","article-title":"Cytokeratin 7 and 20 staining for the diagnosis of lung and colorectal adenocarcinoma","volume":"86","author":"Kummar","year":"2002","journal-title":"Br. J. Cancer,"},{"key":"2021043015503671900_CIT0020","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1309\/2T1Y-7BB7-DAPE-PQ6L","article-title":"Expression of cytokeratins 7 and 20 in ovarian neoplasia","volume":"117","author":"Cathro","year":"2002","journal-title":"Am. J. Clin. Pathol.,"},{"key":"2021043015503671900_CIT0021","doi-asserted-by":"crossref","first-page":"2991","DOI":"10.4161\/cc.7.19.6784","article-title":"Metastasis and AKT activation","volume":"7","author":"Qiao","year":"2008","journal-title":"Cell Cycle,"},{"key":"2021043015503671900_CIT0022","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1093\/annonc\/mdt421","article-title":"ATM down-regulation is associated with poor prognosis in sporadic breast carcinomas","volume":"25","author":"Bueno","year":"2014","journal-title":"Ann. Oncol.,"},{"key":"2021043015503671900_CIT0023","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1158\/1078-0432.CCR-13-1239","article-title":"Having pancreatic cancer with tumoral loss of ATM and normal TP53 protein expression is associated with a poorer prognosis","volume":"20","author":"Kim","year":"2014","journal-title":"Clin. Cancer Res.,"},{"key":"2021043015503671900_CIT0024","doi-asserted-by":"crossref","first-page":"2360","DOI":"10.1091\/mbc.e16-01-0032","article-title":"Hyperactivation of ATM upon DNA-PKcs inhibition modulates p53 dynamics and cell fate in response to DNA damage","volume":"27","author":"Finzel","year":"2016","journal-title":"Mol. Biol. Cell,"},{"key":"2021043015503671900_CIT0025","doi-asserted-by":"crossref","first-page":"11696","DOI":"10.1158\/0008-5472.CAN-07-1610","article-title":"The ataxia telangiectasia-mutated target site Ser18 is required for p53-mediated tumor suppression","volume":"67","author":"Armata","year":"2007","journal-title":"Cancer Res.,"},{"key":"2021043015503671900_CIT0026","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1038\/nature03482","article-title":"DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis","volume":"434","author":"Bartkova","year":"2005","journal-title":"Nature,"},{"key":"2021043015503671900_CIT0027","doi-asserted-by":"crossref","first-page":"62070","DOI":"10.18632\/oncotarget.11386","article-title":"Ataxia-telangiectasia mutated activation mediates tumor necrosis factor-alpha induced MMP-13 up-regulation and metastasis in lung cancer cells","volume":"7","author":"Yan","year":"2016","journal-title":"Oncotarget,"},{"key":"2021043015503671900_CIT0028","doi-asserted-by":"crossref","first-page":"16","DOI":"10.3389\/fonc.2018.00016","article-title":"Role of BRCA mutations in the modulation of response to platinum therapy","volume":"8","author":"Mylavarapu","year":"2018","journal-title":"Front. Oncol.,"},{"key":"2021043015503671900_CIT0029","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/j.ygyno.2019.03.004","article-title":"Increased risk of brain metastases in ovarian cancer patients with BRCA mutations","volume":"153","author":"Ratner","year":"2019","journal-title":"Gynecol. Oncol.,"},{"key":"2021043015503671900_CIT0030","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1002\/cncr.32540","article-title":"Patterns of recurrence and metastasis in BRCA1\/BRCA2-associated breast cancers","volume":"126","author":"Song","year":"2020","journal-title":"Cancer,"}],"container-title":["Carcinogenesis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/carcin\/advance-article-pdf\/doi\/10.1093\/carcin\/bgab002\/36659331\/bgab002.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/carcin\/article-pdf\/42\/4\/640\/37699452\/bgab002.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/carcin\/article-pdf\/42\/4\/640\/37699452\/bgab002.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,30]],"date-time":"2021-04-30T15:57:29Z","timestamp":1619798249000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/carcin\/article\/42\/4\/640\/6071003"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,8]]},"references-count":30,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,1,8]]},"published-print":{"date-parts":[[2021,4,30]]}},"URL":"https:\/\/doi.org\/10.1093\/carcin\/bgab002","relation":{},"ISSN":["0143-3334","1460-2180"],"issn-type":[{"type":"print","value":"0143-3334"},{"type":"electronic","value":"1460-2180"}],"subject":[],"published-other":{"date-parts":[[2021,4,1]]},"published":{"date-parts":[[2021,1,8]]}}}