title: Role of canonical Wnt signaling in endometrial carcinogenesis.
abstract: While the role of Wnt signaling is well established in colorectal carcinogenesis, its function in gynecologic cancers has not been elucidated. Here, we describe the current state of knowledge of canonical Wnt signaling in endometrial cancer (EC), and its implications for future therapeutic targets. Deregulation of the Wnt/β-catenin signaling pathway in EC occurs by inactivating β-catenin mutations in approximately 10-45% of ECs, and via downregulation of Wnt antagonists by epigenetic silencing. The Wnt pathway is intimately involved with estrogen and progesterone, and emerging data implicate it in other important signaling pathways, such as mTOR and Hedgehog. While no therapeutic agents targeting the Wnt signaling pathway are currently in clinical trials, the preclinical data presented suggest a role for Wnt signaling in uterine carcinogenesis, with further research warranted to elucidate the mechanism of action and to proceed towards targeted cancer drug development.
authors.affiliation: Divison of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of California, Irvine, Medical Center, 101 The City Drive, Building 56, Room 260, Orange, CA 92868, USA. tdelling@uci.edu
authors.forename: Thanh H
authors.initials: TH
authors.lastname: Dellinger
authors.forename: Kestutis
authors.initials: K
authors.lastname: Planutis
authors.forename: Krishnansu S
authors.initials: KS
authors.lastname: Tewari
authors.forename: Randall F
authors.initials: RF
authors.lastname: Holcombe
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology*; D017322:Clinical Trials, Phase II as Topic; D004353:Drug Evaluation, Preclinical / Q000379:methods; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D051153:Wnt Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway
chemical_list: D051153:Wnt Proteins