{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T23:47:48Z","timestamp":1791848868361,"version":"4.3.4"},"reference-count":48,"publisher":"Elsevier BV","issue":"6","license":[{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,5,27]],"date-time":"2022-05-27T00:00:00Z","timestamp":1653609600000},"content-version":"vor","delay-in-days":542,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","fertstert.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Fertility and Sterility"],"published-print":{"date-parts":[[2020,12]]},"DOI":"10.1016\/j.fertnstert.2020.06.045","type":"journal-article","created":{"date-parts":[[2020,9,4]],"date-time":"2020-09-04T05:42:50Z","timestamp":1599198170000},"page":"1339-1349","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":21,"title":["Activation of protein kinase B by WNT4 as a regulator of uterine leiomyoma stem cell function"],"prefix":"10.1016","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4369-4589","authenticated-orcid":false,"given":"Shimeng","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariel J.","family":"Dotts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacy A.","family":"Kujawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John S.","family":"Coon V","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Jun","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debabrata","family":"Chakravarti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serdar E.","family":"Bulun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.fertnstert.2020.06.045_bib1","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1126\/science.1112063","article-title":"Uterine fibroids: the elephant in the room","volume":"308","author":"Walker","year":"2005","journal-title":"Science"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib2","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1210\/er.2012-1043","article-title":"Progesterone action in endometrial cancer, endometriosis, uterine fibroids, and breast cancer","volume":"34","author":"Kim","year":"2013","journal-title":"Endocr Rev"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib3","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1056\/NEJMra1209993","article-title":"Uterine fibroids","volume":"369","author":"Bulun","year":"2013","journal-title":"New Engl J Med"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib4","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.fertnstert.2010.08.049","article-title":"Proceedings from the National Institute of Child Health and Human Development conference on the Uterine Fibroid Research Update Workshop","volume":"95","author":"Catherino","year":"2011","journal-title":"Fertil Steril"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib5","doi-asserted-by":"crossref","first-page":"211.e1","DOI":"10.1016\/j.ajog.2011.12.002","article-title":"The estimated annual cost of uterine leiomyomata in the United States","volume":"206","author":"Cardozo","year":"2012","journal-title":"Am J Obstet Gynecol"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib6","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1177\/1933719111432867","article-title":"Medical treatment of uterine leiomyoma","volume":"19","author":"Sabry","year":"2012","journal-title":"Reprod Sci"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib7","doi-asserted-by":"crossref","first-page":"E601","DOI":"10.1210\/jc.2014-2134","article-title":"Human uterine leiomyoma stem\/progenitor cells expressing CD34 and CD49b initiate tumors in\u00a0vivo","volume":"100","author":"Yin","year":"2015","journal-title":"J Clin Endocrinol Metab"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib8","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0036935","article-title":"Role of stem cells in human uterine leiomyoma growth","volume":"7","author":"Ono","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib9","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/j.fertnstert.2012.04.044","article-title":"Identification and characterization of the human leiomyoma side population as putative tumor-initiating cells","volume":"98","author":"Mas","year":"2012","journal-title":"Fertil Steril"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib10","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.fertnstert.2015.04.021","article-title":"Stro-1\/CD44 as putative human myometrial and fibroid stem cell markers","volume":"104","author":"Mas","year":"2015","journal-title":"Fertil Steril"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib11","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1056\/NEJMra061808","article-title":"Cancer Stem Cells","volume":"355","author":"Jordan","year":"2006","journal-title":"New Engl J Med"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib12","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1210\/jc.2016-3497","article-title":"Paracrine pathways in uterine leiomyoma stem cells involve insulinlike growth factor 2 and insulin receptor A","volume":"102","author":"Moravek","year":"2017","journal-title":"J Clin Endocrinol Metab"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib13","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1210\/jc.2017-01585","article-title":"RANKL\/RANK pathway and its inhibitor RANK-Fc in uterine leiomyoma growth","volume":"103","author":"Ikhena","year":"2018","journal-title":"J\u00a0Clin Endocrinol Metab"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib14","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.cell.2006.10.018","article-title":"Wnt\/\u03b2-catenin signaling in development and disease","volume":"127","author":"Clevers","year":"2006","journal-title":"Cell"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib15","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1126\/science.1094291","article-title":"Convergence of Wnt, \u03b2-catenin, and cadherin pathways","volume":"303","author":"Nelson","year":"2004","journal-title":"Science"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib16","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1073\/pnas.1518752113","article-title":"Integrated data analysis reveals uterine leiomyoma subtypes with distinct driver pathways and biomarkers","volume":"113","author":"Mehine","year":"2016","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib17","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1126\/science.1208930","article-title":"MED12, the mediator complex subunit 12 gene, is mutated at high frequency in uterine leiomyomas","volume":"334","author":"Makinen","year":"2011","journal-title":"Science"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib18","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1007\/s43032-019-00084-7","article-title":"Introduction of somatic mutation in MED12 induces Wnt4\/\u03b2-catenin and disrupts autophagy in human uterine myometrial cell","volume":"27","author":"El Andaloussi","year":"2020","journal-title":"Reprod Sci"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib19","first-page":"592","article-title":"Silencing Med12 gene reduces proliferation of human leiomyoma cells mediated via Wnt\/\u03b2-catenin signaling pathway","volume":"158","author":"Al-Hendy","year":"2016","journal-title":"Endocrinology"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib20","doi-asserted-by":"crossref","first-page":"17053","DOI":"10.1073\/pnas.1313650110","article-title":"Paracrine activation of WNT\/\u03b2-catenin pathway in uterine leiomyoma stem cells promotes tumor growth","volume":"110","author":"Ono","year":"2013","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib21","doi-asserted-by":"crossref","first-page":"e1517","DOI":"10.1210\/clinem\/dgz227","article-title":"Activation of \u03b2-catenin signaling and its crosstalk with estrogen and histone deacetylases in human uterine fibroids","volume":"105","author":"Ali","year":"2019","journal-title":"J Clin Endocrinol Metab"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib22","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/nrc839","article-title":"The phosphatidylinositol 3-kinase\u2013AKT pathway in human cancer","volume":"2","author":"Vivanco","year":"2002","journal-title":"Nat Rev Cancer"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib23","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1093\/biolreprod\/81.s1.390","article-title":"Regulation of PI3K\/AKT pathway by progestins in leiomyoma cells [Abstract]","volume":"81(Suppl 1)","author":"Sefton","year":"2009","journal-title":"Biol Reprod"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib24","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1007\/s00109-018-1682-1","article-title":"Oxidative stress-induced miRNAs modulate AKT signaling and promote cellular senescence in uterine leiomyoma","volume":"96","author":"Xu","year":"2018","journal-title":"J Mol Med (Berl)"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib25","doi-asserted-by":"crossref","first-page":"1768","DOI":"10.1210\/jc.2008-2093","article-title":"Progestins activate the AKT pathway in leiomyoma cells and promote survival","volume":"94","author":"Hoekstra","year":"2009","journal-title":"J Clin Endocrinol Metab"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib26","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.1601132","article-title":"Dysfunctional MnSOD leads to redox dysregulation and activation of prosurvival AKT signaling in uterine leiomyomas","volume":"2","author":"Vidimar","year":"2016","journal-title":"Sci Adv"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib27","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.1210\/en.2013-1929","article-title":"Inactivation of AKT induces cellular senescence in uterine leiomyoma","volume":"155","author":"Xu","year":"2014","journal-title":"Endocrinology"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib28","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1002\/gcc.22643","article-title":"Comparative analysis of AKT and the related biomarkers in uterine leiomyomas with MED12, HMGA2, and FH mutations","volume":"57","author":"Xie","year":"2018","journal-title":"Genes Chromosomes Cancer"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib29","doi-asserted-by":"crossref","first-page":"4046","DOI":"10.1210\/en.2013-1389","article-title":"MK-2206, an AKT inhibitor, promotes caspase-independent cell death\u00a0and inhibits leiomyoma growth","volume":"154","author":"Sefton","year":"2013","journal-title":"Endocrinology"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib30","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1210\/en.2017-03191","article-title":"The AKT\/BCL-2 axis mediates survival of uterine leiomyoma in a novel 3D spheroid model","volume":"159","author":"Vidimar","year":"2018","journal-title":"Endocrinology"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib31","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/ng1928","article-title":"PTEN-deficient intestinal stem cells initiate intestinal polyposis","volume":"39","author":"He","year":"2007","journal-title":"Nat Genet"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib32","doi-asserted-by":"crossref","first-page":"11221","DOI":"10.1074\/jbc.M611871200","article-title":"Phosphorylation of beta-catenin by AKT promotes beta-catenin transcriptional activity","volume":"282","author":"Fang","year":"2007","journal-title":"J Biol Chem"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib33","doi-asserted-by":"crossref","first-page":"17479","DOI":"10.1074\/jbc.C000880200","article-title":"Akt participation in the Wnt signaling pathway through dishevelled","volume":"276","author":"Fukumoto","year":"2001","journal-title":"J Biol Chem"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib34","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1083\/jcb.149.7.1433","article-title":"Colocalization and redistribution of dishevelled and actin during WNT-induced mesenchymal morphogenesis","volume":"149","author":"Torres","year":"2000","journal-title":"J Cell Biol"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib35","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1016\/S0006-2952(00)00444-5","article-title":"Integrin-linked kinase (ILK): a \u201chot\u201d therapeutic target","volume":"60","author":"Yoganathan","year":"2000","journal-title":"Biochem Pharmacol"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib36","doi-asserted-by":"crossref","first-page":"2722","DOI":"10.1038\/s41388-018-0612-6","article-title":"Progesterone receptor integrates the effects of mutated MED12 and altered DNA methylation to stimulate RANKL expression and stem cell proliferation in uterine leiomyoma","volume":"38","author":"Liu","year":"2019","journal-title":"Oncogene"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib37","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1101\/gad.230302","article-title":"Axin-mediated CKI phosphorylation of beta-catenin at Ser 45: a molecular switch for the Wnt pathway","volume":"16","author":"Amit","year":"2002","journal-title":"Genes Dev"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib38","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1016\/S0092-8674(02)00685-2","article-title":"Control of \u03b2-catenin phosphorylation\/degradation by a dual-kinase mechanism","volume":"108","author":"Liu","year":"2002","journal-title":"Cell"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib39","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1093\/emboj\/21.7.1733","article-title":"Casein kinase I phosphorylates the Armadillo protein and induces its degradation in Drosophila","volume":"21","author":"Yanagawa","year":"2002","journal-title":"EMBO J"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib40","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.jsbmb.2003.09.007","article-title":"Differential expression of Akt\/protein kinase B, Bcl-2 and Bax proteins in human leiomyoma and myometrium","volume":"87","author":"Kovacs","year":"2003","journal-title":"J Steroid Biochem Mol Biol"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib41","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1095\/biolreprod.108.075648","article-title":"Constitutive activation of beta-catenin in uterine stroma and smooth muscle leads to the development of mesenchymal tumors in mice","volume":"81","author":"Tanwar","year":"2009","journal-title":"Biol Reprod"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib42","doi-asserted-by":"crossref","unstructured":"Ono M, Yin P, Navarro A, Moravek MB, Coon V JS, Druschitz SA, et\u00a0al. Inhibition of canonical WNT signaling attenuates human leiomyoma cell growth. Fertil Steril;101:1441\u20139.e1.","DOI":"10.1016\/j.fertnstert.2014.01.017"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib43","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1093\/oxfordjournals.jbchem.a003276","article-title":"Phosphorylation and regulation of \u03b2-catenin by casein kinase I\u03b5","volume":"132","author":"Sakanaka","year":"2002","journal-title":"J Biochem"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib44","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/43830","article-title":"Casein kinase I transduces Wnt signals","volume":"401","author":"Peters","year":"1999","journal-title":"Nature"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib45","doi-asserted-by":"crossref","first-page":"96","DOI":"10.3389\/fonc.2014.00096","article-title":"The CK1 family: contribution to cellular stress response and its role in carcinogenesis","volume":"4","author":"Knippschild","year":"2014","journal-title":"Front Oncol"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib46","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1042\/BJ20070091","article-title":"Phosphorylation of CK1delta: identification of Ser370 as the major phosphorylation site targeted by PKA in\u00a0vitro and in\u00a0vivo","volume":"406","author":"Giamas","year":"2007","journal-title":"Biochem J"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib47","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.yexcr.2004.04.036","article-title":"Wnt-4 activates the canonical \u03b2-catenin-mediated Wnt pathway\u00a0and binds Frizzled-6 CRD: functional implications of Wnt\/\u03b2-catenin activity in kidney epithelial cells","volume":"298","author":"Lyons","year":"2004","journal-title":"Exp Cell Res"},{"key":"10.1016\/j.fertnstert.2020.06.045_bib48","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1002\/ijc.27424","article-title":"MED12 mutations in uterine fibroids\u2014their relationship to cytogenetic subgroups","volume":"131","author":"Markowski","year":"2012","journal-title":"Int J Cancer"}],"container-title":["Fertility and Sterility"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0015028220306208?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0015028220306208?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T08:28:28Z","timestamp":1758011308000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0015028220306208"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12]]},"references-count":48,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["S0015028220306208"],"URL":"https:\/\/doi.org\/10.1016\/j.fertnstert.2020.06.045","relation":{},"ISSN":["0015-0282"],"issn-type":[{"value":"0015-0282","type":"print"}],"subject":[],"published":{"date-parts":[[2020,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Activation of protein kinase B by WNT4 as a regulator of uterine leiomyoma stem cell function","name":"articletitle","label":"Article Title"},{"value":"Fertility and Sterility","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.fertnstert.2020.06.045","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a92020 American Society for Reproductive Medicine, Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}