{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T06:11:39Z","timestamp":1793686299234,"version":"4.5.1"},"reference-count":55,"publisher":"Springer Science and Business Media LLC","issue":"21","license":[{"start":{"date-parts":[[2021,5,4]],"date-time":"2021-05-04T00:00:00Z","timestamp":1620086400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,5,4]],"date-time":"2021-05-04T00:00:00Z","timestamp":1620086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Oncogene"],"published-print":{"date-parts":[[2021,5,27]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Since cervical cancer still afflicts women around the world, it is necessary to understand the underlying mechanism of cervical cancer development. Infection with HPV is essential for the development of cervical intraepithelial neoplasia (CIN). In addition, estrogen receptor signaling is implicated in the development of cervical cancer. Previously, we have isolated human wings apart-like (WAPL), which is expected to cause chromosomal instability in the process of HPV-infected precancerous lesions to cervical cancer. However, the role of WAPL in the development of CIN is still unknown. In this study, in order to elucidate the role of WAPL in the early lesion, we established WAPL overexpressing mice (WAPL Tg mice) and HPV E6\/E7 knock-in (KI) mice. WAPL Tg mice developed CIN lesion without HPV E6\/E7. Interestingly, in WAPL Tg mice estrogen receptor 1 (ESR1) showed reduction as compared with the wild type, but cell growth factors MYC and Cyclin D1 controlled by ESR1 expressed at high levels. These results suggested that WAPL facilitates sensitivity of ESR1 mediated by some kind of molecule, and as a result, affects the expression of MYC and Cyclin D1 in cervical cancer cells. To detect such molecules, we performed microarray analysis of the uterine cervix in WAPL Tg mice, and focused MACROD1, a co-activator of ESR1. MACROD1 expression was increased in WAPL Tg mice compared with the wild type. In addition, knockdown of WAPL induced the downregulation of MACROD1, MYC, and Cyclin D1 but not ESR1 expression. Furthermore, ESR1 sensitivity assay showed lower activity in WAPL or MACROD1 downregulated cells than control cells. These data suggested that WAPL increases ESR1 sensitivity by activating MACROD1, and induces the expression of MYC and Cyclin D1. Therefore, we concluded that WAPL not only induces chromosomal instability in cervical cancer tumorigenesis, but also plays a key role in activating estrogen receptor signaling in early tumorigenesis.<\/jats:p>","DOI":"10.1038\/s41388-021-01787-5","type":"journal-article","created":{"date-parts":[[2021,5,4]],"date-time":"2021-05-04T19:51:42Z","timestamp":1620157902000},"page":"3695-3706","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["WAPL induces cervical intraepithelial neoplasia modulated with estrogen signaling without HPV E6\/E7"],"prefix":"10.1038","volume":"40","author":[{"given":"Katsuyoshi","family":"Kumagai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7127-1153","authenticated-orcid":false,"given":"Masakatsu","family":"Takanashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1064-4750","authenticated-orcid":false,"given":"Shin-ichiro","family":"Ohno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichirou","family":"Harada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Fujita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiki","family":"Oikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuko","family":"Sudo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun-ichi","family":"Ikeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotaka","family":"Nishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosuke","family":"Oikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7052-4289","authenticated-orcid":false,"given":"Masahiko","family":"Kuroda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,5,4]]},"reference":[{"key":"1787_CR1","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1002\/path.1866","volume":"208","author":"PJ Snijders","year":"2006","unstructured":"Snijders PJ, Steenbergen RD, Heideman DA, Meijer CJ. HPV-mediated cervical carcinogenesis: concepts and clinical implications. J Pathol. 2006;208:152\u201364.","journal-title":"J Pathol."},{"key":"1787_CR2","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1038\/nrc3728","volume":"14","author":"RD Steenbergen","year":"2014","unstructured":"Steenbergen RD, Snijders PJ, Heideman DA, Meijer CJ. Clinical implications of (epi)genetic changes in HPV-induced cervical precancerous lesions. Nat Rev Cancer. 2014;14:395\u2013405.","journal-title":"Nat Rev Cancer."},{"key":"1787_CR3","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1038\/nrc798","volume":"2","author":"H Harald zur","year":"2002","unstructured":"Harald zur H. Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer. 2002;2:342\u201350.","journal-title":"Nat Rev Cancer."},{"key":"1787_CR4","doi-asserted-by":"publisher","first-page":"1505","DOI":"10.1111\/j.1349-7006.2007.00546.x","volume":"98","author":"M Narisawa-Saito","year":"2007","unstructured":"Narisawa-Saito M, Kiyono T. Basic mechanisms of high-risk human papillomavirus-induced carcinogenesis: roles of E6 and E7 proteins. Cancer Sci. 2007;98:1505\u201311.","journal-title":"Cancer Sci."},{"key":"1787_CR5","doi-asserted-by":"publisher","first-page":"3545","DOI":"10.1158\/0008-5472.CAN-03-3822","volume":"64","author":"K Oikawa","year":"2004","unstructured":"Oikawa K, Ohbayashi T, Kiyono T, Nishi H, Isaka K, Umezawa A, et al. Expression of a novel human gene, human wings apart-like (hWAPL), is associated with cervical carcinogenesis and tumor progression. Cancer Res. 2004;64:3545\u20139.","journal-title":"Cancer Res."},{"key":"1787_CR6","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1038\/sj.bjc.6602329","volume":"92","author":"M Kuroda","year":"2005","unstructured":"Kuroda M, Kiyono T, Oikawa K, Yoshida K, Mukai K. The human papillomavirus E6 and E7 inducible oncogene, hWAPL, exhibits potential as a therapeutic target. Br J Cancer. 2005;92:290\u20133.","journal-title":"Br J Cancer."},{"key":"1787_CR7","doi-asserted-by":"publisher","first-page":"2406","DOI":"10.1016\/j.cub.2006.10.061","volume":"16","author":"R Gandhi","year":"2006","unstructured":"Gandhi R, Gillespie PJ, Hirano T. Human Wapl is a cohesin-binding protein that promotes sister-chromatid resolution in mitotic prophase. Curr Biol. 2006;16:2406\u201317.","journal-title":"Curr Biol."},{"key":"1787_CR8","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1016\/j.cell.2006.09.040","volume":"127","author":"S Kueng","year":"2006","unstructured":"Kueng S, Hegemann B, Peters BH, Lipp JJ, Schleiffer A, Mechtler K, et al. Wapl controls the dynamic association of cohesin with chromatin. Cell. 2006;127:955\u201367.","journal-title":"Cell."},{"key":"1787_CR9","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1016\/j.cell.2010.10.031","volume":"143","author":"T Nishiyama","year":"2010","unstructured":"Nishiyama T, Ladurner R, Schmitz J, Kreidl E, Schleiffer A, Bhaskara V, et al. Sororin mediates sister chromatid cohesion by antagonizing Wapl. Cell. 2010;143:737\u201349.","journal-title":"Cell."},{"key":"1787_CR10","doi-asserted-by":"publisher","first-page":"2073","DOI":"10.4161\/cc.20241","volume":"11","author":"N Zhang","year":"2012","unstructured":"Zhang N, Pati D. Sororin is a master regulator of sister chromatid cohesion and separation. Cell Cycle. 2012;11:2073\u201383.","journal-title":"Cell Cycle."},{"key":"1787_CR11","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1038\/nsmb.2880","volume":"21","author":"K Hara","year":"2014","unstructured":"Hara K, Zheng G, Qu Q, Liu H, Ouyang Z, Chen Z, et al. Structure of cohesin subcomplex pinpoints direct shugoshin-Wapl antagonism in centromeric cohesion. Nat Struct Mol Biol. 2014;21:864\u201370.","journal-title":"Nat Struct Mol Biol."},{"key":"1787_CR12","doi-asserted-by":"publisher","first-page":"635","DOI":"10.15252\/embj.201592532","volume":"35","author":"R Ladurner","year":"2016","unstructured":"Ladurner R, Kreidl E, Ivanov MP, Ekker H, Idarraga-Amado MH, Busslinger GA, et al. Sororin actively maintains sister chromatid cohesion. EMBO J. 2016;35:635\u201353.","journal-title":"EMBO J."},{"key":"1787_CR13","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1016\/j.bbrc.2007.03.037","volume":"356","author":"T Ohbayashi","year":"2007","unstructured":"Ohbayashi T, Oikawa K, Yamada K, Nishida-Umehara C, Matsuda Y, Satoh H, et al. Unscheduled overexpression of human WAPL promotes chromosomal instability. Biochem Biophys Res Commun. 2007;356:699\u2013704.","journal-title":"Biochem Biophys Res Commun."},{"key":"1787_CR14","doi-asserted-by":"publisher","first-page":"2930","DOI":"10.1073\/pnas.93.7.2930","volume":"93","author":"JM Arbeit","year":"1996","unstructured":"Arbeit JM, Howley PM, Hanahan D. Chronic estrogen-induced cervical and vaginal squamous carcinogenesis in human papillomavirus type 16 transgenic mice. Proc Natl Acad Sci USA. 1996;93:2930\u20135.","journal-title":"Proc Natl Acad Sci USA."},{"key":"1787_CR15","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1016\/j.tem.2010.03.005","volume":"21","author":"SH Chung","year":"2010","unstructured":"Chung SH, Franceschi S, Lambert PF. Estrogen and ERalpha: culprits in cervical cancer? Trends Endocrinol Metab. 2010;21:504\u201311.","journal-title":"Trends Endocrinol Metab."},{"key":"1787_CR16","doi-asserted-by":"publisher","first-page":"19467","DOI":"10.1073\/pnas.0911436106","volume":"106","author":"SH Chung","year":"2009","unstructured":"Chung SH, Lambert PF. Prevention and treatment of cervical cancer in mice using estrogen receptor antagonists. Proc Natl Acad Sci USA. 2009;106:19467\u201372.","journal-title":"Proc Natl Acad Sci USA."},{"key":"1787_CR17","doi-asserted-by":"publisher","first-page":"9928","DOI":"10.1158\/0008-5472.CAN-08-2051","volume":"68","author":"SH Chung","year":"2008","unstructured":"Chung SH, Wiedmeyer K, Shai A, Korach KS, Lambert PF. Requirement for estrogen receptor alpha in a mouse model for human papillomavirus-associated cervical cancer. Cancer Res. 2008;68:9928\u201334.","journal-title":"Cancer Res."},{"key":"1787_CR18","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1093\/carcin\/bgt350","volume":"35","author":"J Son","year":"2014","unstructured":"Son J, Park JW, Lambert PF, Chung SH. Requirement of estrogen receptor alpha DNA-binding domain for HPV oncogene-induced cervical carcinogenesis in mice. Carcinogenesis. 2014;35:489\u201396.","journal-title":"Carcinogenesis."},{"key":"1787_CR19","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1002\/path.5069","volume":"245","author":"J Son","year":"2018","unstructured":"Son J, Park Y, Chung SH. Epithelial oestrogen receptor \u03b1 is dispensable for the development of oestrogen-induced cervical neoplastic diseases. J Pathol. 2018;245:147\u201352.","journal-title":"J Pathol."},{"key":"1787_CR20","doi-asserted-by":"publisher","first-page":"884","DOI":"10.2353\/ajpath.2010.091166","volume":"177","author":"Y Zhai","year":"2010","unstructured":"Zhai Y, Bommer GT, Feng Y, Wiese AB, Fearon ER, Cho KR. Loss of estrogen receptor 1 enhances cervical cancer invasion. Am J Pathol. 2010;177:884\u201395.","journal-title":"Am J Pathol."},{"key":"1787_CR21","first-page":"153","volume":"26","author":"A Kwasniewska","year":"2011","unstructured":"Kwasniewska A, Postawski K, Gozdzicka-Jozefiak A, Kwasniewski W, Grywalska E, Zdunek M, et al. Estrogen and progesterone receptor expression in HPV-positive and HPV-negative cervical carcinomas. Oncol Rep. 2011;26:153\u201360.","journal-title":"Oncol Rep."},{"key":"1787_CR22","doi-asserted-by":"crossref","first-page":"E3255","DOI":"10.1073\/pnas.1509322112","volume":"112","author":"JA den Boon","year":"2015","unstructured":"den Boon JA, Pyeon D, Wang SS, Horswill M, Schiffman M, Sherman M, et al. Molecular transitions from papillomavirus infection to cervical precancer and cancer: role of stromal estrogen receptor signaling. Proc Natl Acad Sci USA. 2015;112:E3255\u201364.","journal-title":"Proc Natl Acad Sci USA."},{"key":"1787_CR23","doi-asserted-by":"publisher","first-page":"1247","DOI":"10.1097\/IGC.0000000000001004","volume":"27","author":"MK Hong","year":"2017","unstructured":"Hong MK, Wang JH, Su CC, Li MH, Hsu YH, Chu TY. Expression of estrogen and progesterone receptor in tumor stroma predicts favorable prognosis of cervical squamous cell carcinoma. Int J Gynecol Cancer. 2017;27:1247\u201355.","journal-title":"Int J Gynecol Cancer."},{"key":"1787_CR24","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1677\/ERC-06-0082","volume":"14","author":"WD Han","year":"2007","unstructured":"Han WD, Zhao YL, Meng YG, Zang L, Wu ZQ, Li Q, et al. Estrogenically regulated LRP16 interacts with estrogen receptor alpha and enhances the receptor\u2019s transcriptional activity. Endocr Relat Cancer. 2007;14:741\u201353.","journal-title":"Endocr Relat Cancer."},{"key":"1787_CR25","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1677\/JOE-09-0054","volume":"202","author":"L Tian","year":"2009","unstructured":"Tian L, Wu Z, Zhao Y, Meng Y, Si Y, Fu X, et al. Differential induction of LRP16 by liganded and unliganded estrogen receptor alpha in SKOV3 ovarian carcinoma cells. J Endocrinol. 2009;202:167\u201377.","journal-title":"J Endocrinol."},{"key":"1787_CR26","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1177\/0023677215617387","volume":"50","author":"C Merkwitz","year":"2016","unstructured":"Merkwitz C, Blaschuk O, Eplinius F, Winkler J, Pr\u00f6mel S, Schulz A, et al. A simple method for inducing estrous cycle stage-specific morphological changes in the vaginal epithelium of immature female mice. Lab Anim. 2016;50:344\u201353.","journal-title":"Lab Anim."},{"key":"1787_CR27","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1002\/bdrb.20106","volume":"80","author":"JM Goldman","year":"2007","unstructured":"Goldman JM, Murr AS, Cooper RL. The rodent estrous cycle: characterization of vaginal cytology and its utility in toxicological studies. Birth Defects Res B Dev Reprod Toxicol. 2007;80:84\u201397.","journal-title":"Birth Defects Res B Dev Reprod Toxicol."},{"key":"1787_CR28","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1002\/bdrb.20120","volume":"80","author":"S Li","year":"2007","unstructured":"Li S, Davis B. Evaluating rodent vaginal and uterine histology in toxicity studies. Birth Defects Res B Dev Reprod Toxicol. 2007;80:246\u201352.","journal-title":"Birth Defects Res B Dev Reprod Toxicol."},{"key":"1787_CR29","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.diff.2010.06.007","volume":"80","author":"T Kurita","year":"2010","unstructured":"Kurita T. Developmental origin of vaginal epithelium. Differentiation. 2010;80:99\u2013105.","journal-title":"Differentiation."},{"key":"1787_CR30","doi-asserted-by":"publisher","first-page":"162","DOI":"10.3802\/jgo.2008.19.3.162","volume":"19","author":"EJ Nam","year":"2008","unstructured":"Nam EJ, Kim JW, Hong JW, Jang HS, Lee SY, Jang SY, et al. Expression of the p16 and Ki-67 in relation to the grade of cervical intraepithelial neoplasia and high-risk human papillomavirus infection. J Gynecol Oncol. 2008;19:162\u20138.","journal-title":"J Gynecol Oncol."},{"key":"1787_CR31","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1016\/j.ctrv.2008.10.005","volume":"35","author":"I Tsoumpou","year":"2009","unstructured":"Tsoumpou I, Arbyn M, Kyrgiou M, Wentzensen N, Koliopoulos G, Martin-Hirsch P, et al. p16 (INK4a) immunostaining in cytological and histological specimens from the uterine cervix: a systematic review and meta-analysis. Cancer Treat Rev. 2009;35:210\u201320.","journal-title":"Cancer Treat Rev."},{"key":"1787_CR32","first-page":"2979","volume":"8","author":"P Zhong","year":"2015","unstructured":"Zhong P, Li J, Gu Y, Liu Y, Wang A, Sun Y, et al. P16 and Ki-67 expression improves the diagnostic accuracy of cervical lesions but not predict persistent high risk human papillomavirus infection with CIN1. Int J Clin Exp Pathol. 2015;8:2979\u201386.","journal-title":"Int J Clin Exp Pathol."},{"key":"1787_CR33","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1186\/s12985-019-1225-6","volume":"16","author":"Y Li","year":"2019","unstructured":"Li Y, Liu J, Gong L, Sun X, Long W, Combining HPV. DNA load with p16\/Ki-67 staining to detect cervical precancerous lesions and predict the progression of CIN1-2 lesions. Virol J. 2019;16:117.","journal-title":"Virol J."},{"key":"1787_CR34","doi-asserted-by":"publisher","first-page":"S47","DOI":"10.1677\/erc.1.00993","volume":"12","author":"AJ Butt","year":"2005","unstructured":"Butt AJ, McNeil CM, Musgrove EA, Sutherland RL. Downstream targets of growth factor and oestrogen signalling and endocrine resistance: the potential roles of c-Myc, cyclin D1 and cyclin E. Endocr Relat Cancer. 2005;12:S47\u201359.","journal-title":"Endocr Relat Cancer."},{"key":"1787_CR35","first-page":"1695","volume":"125","author":"XJ Li","year":"2012","unstructured":"Li XJ, Guo QH, Wang X, Xue B, Sun LQ, Meng QT, et al. LRP16 gene protects mouse insulinoma MIN6 cells against fatty acid-induced apoptosis through Akt\/FoxO1 signaling. Chin Med J. 2012;125:1695\u2013702.","journal-title":"Chin Med J."},{"key":"1787_CR36","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1016\/0092-8674(93)90384-3","volume":"75","author":"M Scheffner","year":"1993","unstructured":"Scheffner M, Huibregtse JM, Vierstra RD, Howley PM. The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53. Cell. 1993;75:495\u2013505.","journal-title":"Cell."},{"key":"1787_CR37","doi-asserted-by":"publisher","first-page":"4549","DOI":"10.1073\/pnas.89.10.4549","volume":"89","author":"S Chellappan","year":"1992","unstructured":"Chellappan S, Kraus VB, Kroger B, Howley PM, Phelps WC, Nevins JR. Adenovirus E1A, simian virus 40 tumor antigen, and human papillomavirus E7 protein share the capacity to disrupt the interaction between transcription factor E2F and the retinoblastoma gene product. Proc Natl Acad Sci USA. 1992;89:4549\u201353.","journal-title":"Proc Natl Acad Sci USA."},{"key":"1787_CR38","first-page":"7075","volume":"62","author":"S Duensing","year":"2002","unstructured":"Duensing S, M\u00fcnger K. The human papillomavirus type 16 E6 and E7 oncoproteins independently induce numerical and structural chromosome instability. Cancer Res. 2002;62:7075\u201382.","journal-title":"Cancer Res."},{"key":"1787_CR39","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1002\/ijc.11691","volume":"109","author":"S Duensing","year":"2004","unstructured":"Duensing S, M\u00fcnger K. Mechanisms of genomic instability in human cancer: insights from studies with human papillomavirus oncoproteins. Int J Cancer. 2004;109:157\u201362.","journal-title":"Int J Cancer."},{"key":"1787_CR40","first-page":"4862","volume":"63","author":"RR Riley","year":"2003","unstructured":"Riley RR, Duensing S, Brake T, M\u00fcnger K, Lambert PF, Arbeit JM. Dissection of human papillomavirus E6 and E7 function in transgenic mouse models of cervical carcinogenesis. Cancer Res. 2003;63:4862\u201371.","journal-title":"Cancer Res."},{"key":"1787_CR41","doi-asserted-by":"publisher","first-page":"1626","DOI":"10.1158\/0008-5472.CAN-06-3344","volume":"67","author":"A Shai","year":"2007","unstructured":"Shai A, Brake T, Somoza C, Lambert PF. The human papillomavirus E6 oncogene dysregulates the cell cycle and contributes to cervical carcinogenesis through two independent activities. Cancer Res. 2007;67:1626\u201335.","journal-title":"Cancer Res."},{"key":"1787_CR42","doi-asserted-by":"publisher","first-page":"2794","DOI":"10.1111\/cas.14140","volume":"110","author":"M Chen","year":"2019","unstructured":"Chen M, Li L, Zheng PS. SALL4 promotes the tumorigenicity of cervical cancer cells through activation of the Wnt\/\u03b2-catenin pathway via CTNNB1. Cancer Sci. 2019;110:2794\u2013805.","journal-title":"Cancer Sci."},{"key":"1787_CR43","doi-asserted-by":"publisher","first-page":"1170","DOI":"10.1056\/NEJMc1308785","volume":"369","author":"E Suzuki","year":"2013","unstructured":"Suzuki E, Chiba T, Yokosuka O. Oncofetal gene SALL4 in aggressive hepatocellular carcinoma. N Engl J Med. 2013;369:1170\u20131.","journal-title":"N Engl J Med."},{"key":"1787_CR44","doi-asserted-by":"publisher","first-page":"75425","DOI":"10.18632\/oncotarget.12251","volume":"7","author":"KJ Yong","year":"2016","unstructured":"Yong KJ, Li A, Ou WB, Hong CKY, Zhao W, Wang F, et al. Targeting SALL4 by entinostat in lung cancer. Oncotarget. 2016;7:75425\u201340.","journal-title":"Oncotarget."},{"key":"1787_CR45","doi-asserted-by":"publisher","DOI":"10.1038\/oncsis.2016.69","volume":"5","author":"X Yuan","year":"2016","unstructured":"Yuan X, Zhang X, Zhang W, Liang W, Zhang P, Shi H, et al. SALL4 promotes gastric cancer progression through activating CD44 expression. Oncogenesis. 2016;5:e268.","journal-title":"Oncogenesis."},{"key":"1787_CR46","first-page":"933","volume":"38","author":"D Kobayashi","year":"2011","unstructured":"Kobayashi D, Kuribayshi K, Tanaka M, Watanabe N. SALL4 is essential for cancer cell proliferation and is overexpressed at early clinical stages in breast cancer. Int J Oncol. 2011;38:933\u20139.","journal-title":"Int J Oncol."},{"key":"1787_CR47","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1038\/onc.2013.529","volume":"34","author":"A Li","year":"2015","unstructured":"Li A, Jiao Y, Yong KJ, Wang F, Gao C, Yan B, et al. SALL4 is a new target in endometrial cancer. Oncogene. 2015;34:63\u201372.","journal-title":"Oncogene."},{"key":"1787_CR48","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1016\/j.ajpath.2012.04.008","volume":"181","author":"TT Gu","year":"2012","unstructured":"Gu TT, Liu SY, Zheng PS. Cytoplasmic NANOG-positive stromal cells promote human cervical cancer progression. Am J Pathol. 2012;181:652\u201361.","journal-title":"Am J Pathol."},{"key":"1787_CR49","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2013.272","volume":"4","author":"YD Wang","year":"2013","unstructured":"Wang YD, Cai N, Wu XL, Cao HZ, Xie LL, Zheng PS. OCT4 promotes tumorigenesis and inhibits apoptosis of cervical cancer cells by miR-125b\/BAK1 pathway. Cell Death Dis. 2013;4:e760.","journal-title":"Cell Death Dis."},{"key":"1787_CR50","doi-asserted-by":"publisher","first-page":"9092","DOI":"10.18632\/oncotarget.2377","volume":"5","author":"Q Chen","year":"2014","unstructured":"Chen Q, Cao HZ, Zheng PS. LGR5 promotes the proliferation and tumor formation of cervical cancer cells through the Wnt\/\u03b2-catenin signaling pathway. Oncotarget. 2014;5:9092\u2013105.","journal-title":"Oncotarget."},{"key":"1787_CR51","doi-asserted-by":"publisher","first-page":"36115","DOI":"10.18632\/oncotarget.8741","volume":"7","author":"Q Chen","year":"2016","unstructured":"Chen Q, Zheng PS, Yang WT. EZH2-mediated repression of GSK-3\u03b2 and TP53 promotes Wnt\/\u03b2-catenin signaling-dependent cell expansion in cervical carcinoma. Oncotarget. 2016;7:36115\u201329.","journal-title":"Oncotarget."},{"key":"1787_CR52","doi-asserted-by":"publisher","first-page":"225","DOI":"10.5483\/BMBRep.2018.51.5.045","volume":"51","author":"K Hong","year":"2018","unstructured":"Hong K, Choi Y. Role of estrogen and RAS signaling in repeated implantation failure. BMB Rep. 2018;51:225\u20139.","journal-title":"BMB Rep."},{"key":"1787_CR53","doi-asserted-by":"publisher","first-page":"12986","DOI":"10.1073\/pnas.1513550112","volume":"112","author":"S Miyagawa","year":"2015","unstructured":"Miyagawa S, Iguchi T. Epithelial estrogen receptor 1 intrinsically mediates squamous differentiation in the mouse vagina. Proc Natl Acad Sci USA. 2015;112:12986\u201391.","journal-title":"Proc Natl Acad Sci USA."},{"key":"1787_CR54","doi-asserted-by":"publisher","first-page":"2490","DOI":"10.1073\/pnas.0409883102","volume":"102","author":"T Brake","year":"2005","unstructured":"Brake T, Lambert PF. Estrogen contributes to the onset, persistence, and malignant progression of cervical cancer in a human papillomavirus-transgenic mouse model. Proc Natl Acad Sci USA. 2005;102:2490\u20135.","journal-title":"Proc Natl Acad Sci USA."},{"key":"1787_CR55","doi-asserted-by":"publisher","first-page":"2591","DOI":"10.1159\/000495931","volume":"51","author":"L Zang","year":"2018","unstructured":"Zang L, Hong Q, Yang G, Gu W, Wang A, Dou J, et al. MACROD1\/LRP16 enhances LPS-stimulated inflammatory responses by up-regulating a Rac1-dependent pathway in adipocytes. Cell Physiol Biochem. 2018;51:2591\u2013603.","journal-title":"Cell Physiol Biochem."}],"container-title":["Oncogene"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41388-021-01787-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41388-021-01787-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41388-021-01787-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T10:39:07Z","timestamp":1675247947000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41388-021-01787-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,4]]},"references-count":55,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2021,5,27]]}},"alternative-id":["1787"],"URL":"https:\/\/doi.org\/10.1038\/s41388-021-01787-5","relation":{},"ISSN":["0950-9232","1476-5594"],"issn-type":[{"value":"0950-9232","type":"print"},{"value":"1476-5594","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,4]]},"assertion":[{"value":"21 August 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 March 2021","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 April 2021","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 May 2021","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}