title: The evolving roles of canonical WNT signaling in stem cells and tumorigenesis: implications in targeted cancer therapies.
abstract: The canonical WNT/β-catenin signaling pathway governs a myriad of biological processes underlying the development and maintenance of adult tissue homeostasis, including regulation of stem cell self-renewal, cell proliferation, differentiation, and apoptosis. WNTs are secreted lipid-modified glycoproteins that act as short-range ligands to activate receptor-mediated signaling pathways. The hallmark of the canonical pathway is the activation of β-catenin-mediated transcriptional activity. Canonical WNTs control the β-catenin dynamics as the cytoplasmic level of β-catenin is tightly regulated via phosphorylation by the 'destruction complex', consisting of glycogen synthase kinase 3β (GSK3β), casein kinase 1α (CK1α), the scaffold protein AXIN, and the tumor suppressor adenomatous polyposis coli (APC). Aberrant regulation of this signaling cascade is associated with varieties of human diseases, especially cancers. Over the past decade, significant progress has been made in understanding the mechanisms of canonical WNT signaling. In this review, we focus on the current understanding of WNT signaling at the extracellular, cytoplasmic membrane, and intracellular/nuclear levels, including the emerging knowledge of cross-talk with other pathways. Recent progresses in developing novel WNT pathway-targeted therapies will also be reviewed. Thus, this review is intended to serve as a refresher of the current understanding about the physiologic and pathogenic roles of WNT/β-catenin signaling pathway, and to outline potential therapeutic opportunities by targeting the canonical WNT pathway.
authors.affiliation: Stem Cell Biology and Therapy Laboratory, Ministry of Education Key Laboratory of Child Development and Disorders, The Children's Hospital, Chongqing Medical University, Chongqing, China.|Molecular Oncology Laboratory, The University of Chicago Medical Center, Chicago, IL, USA.|Chongqing Stem Cell Therapy Engineering and Technology Center, Chongqing, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Yang
authors.affiliation: Molecular Oncology Laboratory, The University of Chicago Medical Center, Chicago, IL, USA.|Department of Surgery, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Molecular Oncology Laboratory, The University of Chicago Medical Center, Chicago, IL, USA.|Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, and the Affiliated Hospital of Stomatology of Chongqing Medical University, Chongqing, China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Stem Cell Biology and Therapy Laboratory, Ministry of Education Key Laboratory of Child Development and Disorders, The Children's Hospital, Chongqing Medical University, Chongqing, China.|Molecular Oncology Laboratory, The University of Chicago Medical Center, Chicago, IL, USA.
authors.forename: Zhongliang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Stem Cell Biology and Therapy Laboratory, Ministry of Education Key Laboratory of Child Development and Disorders, The Children's Hospital, Chongqing Medical University, Chongqing, China.|Molecular Oncology Laboratory, The University of Chicago Medical Center, Chicago, IL, USA.
authors.forename: Guoxin
authors.initials: G
authors.lastname: Nan
authors.affiliation: Stem Cell Biology and Therapy Laboratory, Ministry of Education Key Laboratory of Child Development and Disorders, The Children's Hospital, Chongqing Medical University, Chongqing, China.|Molecular Oncology Laboratory, The University of Chicago Medical Center, Chicago, IL, USA.
authors.forename: Yasha
authors.initials: Y
authors.lastname: Li
authors.affiliation: Molecular Oncology Laboratory, The University of Chicago Medical Center, Chicago, IL, USA.|Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, and the Affiliated Hospital of Stomatology of Chongqing Medical University, Chongqing, China.
authors.forename: Fugui
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Molecular Oncology Laboratory, The University of Chicago Medical Center, Chicago, IL, USA.
authors.forename: Maryam K
authors.initials: MK
authors.lastname: Mohammed
authors.affiliation: Molecular Oncology Laboratory, The University of Chicago Medical Center, Chicago, IL, USA.
authors.forename: Rex C
authors.initials: RC
authors.lastname: Haydon
authors.affiliation: Molecular Oncology Laboratory, The University of Chicago Medical Center, Chicago, IL, USA.
authors.forename: Hue H
authors.initials: HH
authors.lastname: Luu
authors.affiliation: Stem Cell Biology and Therapy Laboratory, Ministry of Education Key Laboratory of Child Development and Disorders, The Children's Hospital, Chongqing Medical University, Chongqing, China.|Molecular Oncology Laboratory, The University of Chicago Medical Center, Chicago, IL, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Bi
authors.affiliation: Stem Cell Biology and Therapy Laboratory, Ministry of Education Key Laboratory of Child Development and Disorders, The Children's Hospital, Chongqing Medical University, Chongqing, China.|Molecular Oncology Laboratory, The University of Chicago Medical Center, Chicago, IL, USA.|Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, and the Affiliated Hospital of Stomatology of Chongqing Medical University, Chongqing, China.
authors.forename: Tong-Chuan
authors.initials: TC
authors.lastname: He
mesh_terms: D000818:Animals; D063646:Carcinogenesis; D055808:Drug Discovery; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy*; D013234:Stem Cells; D051153:Wnt Proteins; D060449:Wnt Signaling Pathway
chemical_list: D051153:Wnt Proteins