{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T15:54:55Z","timestamp":1776700495894,"version":"3.51.2"},"reference-count":56,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,8,21]],"date-time":"2020-08-21T00:00:00Z","timestamp":1597968000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP20cm0106114"],"award-info":[{"award-number":["JP20cm0106114"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17H01400"],"award-info":[{"award-number":["17H01400"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["26114005"],"award-info":[{"award-number":["26114005"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["26640081"],"award-info":[{"award-number":["26640081"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cervical cancer (CC) is usually initiated by infection with high\u2010risk types of human papillomavirus (HPV). The HPV E6 and E7 proteins target p53 and RB, respectively, but other cellular targets likely exist. We generated uterus\u2010specific MOB1A\/B double KO (u<jats:italic>Mob1<\/jats:italic>DKO) mice, which immediately developed cervical squamous cell carcinoma in situ. Mutant cervical epithelial cells showed YAP1\u2010dependent hyperproliferation, altered self\u2010renewal, impaired contact inhibition, and chromosomal instability. p53 activation was increased in u<jats:italic>Mob1<\/jats:italic>DKO cells, and additional p53 loss in u<jats:italic>Mob1<\/jats:italic>DKO mice accelerated tumor invasion. In human CC, strong YAP1 activation was observed from the precancerous stage. Human cells overexpressing HPV16 E6\/E7 showed inactivation of not only p53 and RB but also PTPN14, boosting YAP1 activation. Estrogen, cigarette smoke condensate, and PI3K hyperactivation all increased YAP1 activity in human cervical epithelial cells, and PTPN14 depletion along with PI3K activation or estrogen treatment further enhanced YAP1. Thus, immediate CC onset may initiate when YAP1 activity exceeds an oncogenic threshold, making Hippo\u2010YAP1 signaling a major CC driver.<\/jats:p>","DOI":"10.1111\/cas.14581","type":"journal-article","created":{"date-parts":[[2020,7,27]],"date-time":"2020-07-27T10:40:33Z","timestamp":1595846433000},"page":"3576-3587","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Endogenous YAP1 activation drives immediate onset of cervical carcinoma in situ in mice"],"prefix":"10.1111","volume":"111","author":[{"given":"Miki","family":"Nishio","sequence":"first","affiliation":[{"name":"Division of Molecular and Cellular Biology Kobe University Graduate School of Medicine Kobe Japan"},{"name":"Division of Cancer Genetics MIB Kyushu University Fukuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoko","family":"To","sequence":"additional","affiliation":[{"name":"Division of Cancer Genetics MIB Kyushu University Fukuoka Japan"},{"name":"Department of Obstetrics and Gynecology Faculty of Life Sciences Kumamoto University Kumamoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomohiko","family":"Maehama","sequence":"additional","affiliation":[{"name":"Division of Molecular and Cellular Biology Kobe University Graduate School of Medicine Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukari","family":"Aono","sequence":"additional","affiliation":[{"name":"Division of Molecular and Cellular Biology Kobe University Graduate School of Medicine Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junji","family":"Otani","sequence":"additional","affiliation":[{"name":"Division of Molecular and Cellular Biology Kobe University Graduate School of Medicine Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroki","family":"Hikasa","sequence":"additional","affiliation":[{"name":"Department of Biochemistry School of Medicine University of Occupational and Environmental Health Kita\u2010kyushu Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akihiro","family":"Kitagawa","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery Medical School and Graduate School of Frontier Biosciences Osaka University Suita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3897-9974","authenticated-orcid":false,"given":"Koshi","family":"Mimori","sequence":"additional","affiliation":[{"name":"Department of Surgery Kyushu University Beppu Hospital Beppu Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takehiko","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Department of Biochemical Pathophysiology MRI Tokyo Medical and Dental University Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Nishina","sequence":"additional","affiliation":[{"name":"Department of Developmental and Regenerative Biology MRI Tokyo Medical and Dental University Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5757-1109","authenticated-orcid":false,"given":"Shinya","family":"Toyokuni","sequence":"additional","affiliation":[{"name":"Department of Pathology and Biological Responses Graduate School of Medicine Nagoya University Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John P.","family":"Lydon","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology Baylor College of Medicine Houston TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuwa","family":"Nakao","sequence":"additional","affiliation":[{"name":"MIC Graduate School of Medicine Kyoto University Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tak","family":"Wah Mak","sequence":"additional","affiliation":[{"name":"The Princess Margaret Cancer Centre UHN Toronto ON Canada"},{"name":"Department of Medical Biophysics Toronto University Toronto ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1769-403X","authenticated-orcid":false,"given":"Tohru","family":"Kiyono","sequence":"additional","affiliation":[{"name":"Division of Carcinogenesis and Cancer Prevention National Cancer Center Research Institute Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hidetaka","family":"Katabuchi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Faculty of Life Sciences Kumamoto University Kumamoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6236-2849","authenticated-orcid":false,"given":"Hironori","family":"Tashiro","sequence":"additional","affiliation":[{"name":"Department of Women's Health Sciences Faculty of Life Sciences Kumamoto University Kumamoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5950-8808","authenticated-orcid":false,"given":"Akira","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Division of Molecular and Cellular Biology Kobe University Graduate School of Medicine Kobe Japan"},{"name":"Division of Cancer Genetics MIB Kyushu University Fukuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,8,21]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa021641"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/00130404-200309000-00003"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.31231"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21492"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2011.01.003"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(08)70103-7"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32470-X"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.3332\/ecancer.2015.533"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90529-8"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2537532"},{"key":"e_1_2_8_12_1","first-page":"4620","article-title":"E7 protein of human papilloma virus\u201016 induces degradation of retinoblastoma protein through the ubiquitin\u2010proteasome pathway","volume":"56","author":"Boyer SN","year":"1996","journal-title":"Cancer Res"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-12-2083"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-5266"},{"key":"e_1_2_8_15_1","first-page":"237","article-title":"Targeting the Hippo signalling pathway for cancer treatment","volume":"161","author":"Nakatani K","year":"2017","journal-title":"J Biochem"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M102398200"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C110.212621"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.02.031"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.192955.112"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2884"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1843810"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA118.002715"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.13318"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1664408"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature21386"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/cjp2.27"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04590-1"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI79573"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2018.01.003"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/v7072785"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2443.2006.00954.x"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01530-16"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2017.09.007"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/celldisc.2016.21"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.1844"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2017.6180"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1097\/IGC.0000000000000259"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.02.004"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1097\/IGC.0b013e31828c8619"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/gene.20098"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8668"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1517188113"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.02119-06"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0090836"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1216462110"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.68.7.4358-4368.1994"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3458"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-8258(02)00106-3"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0147029"},{"key":"e_1_2_8_50_1","first-page":"2439","article-title":"Natural history of squamous intraepithelial lesions in pregnancy and mode of delivery","volume":"38","author":"Schuster S","year":"2018","journal-title":"Anticancer Res"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2010.03.005"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.5402\/2011\/847684"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.03022"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(02)00776-1"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aay3324"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.2005.027839"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.31557\/APJCP.2019.20.2.549"}],"container-title":["Cancer Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcas.14581","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.14581","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cas.14581","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.14581","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T10:24:44Z","timestamp":1739269484000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cas.14581"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,21]]},"references-count":56,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2020,10]]}},"alternative-id":["10.1111\/cas.14581"],"URL":"https:\/\/doi.org\/10.1111\/cas.14581","archive":["Portico"],"relation":{},"ISSN":["1347-9032","1349-7006"],"issn-type":[{"value":"1347-9032","type":"print"},{"value":"1349-7006","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,21]]},"assertion":[{"value":"2020-05-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-07-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-08-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}