title: Vangl1 and Vangl2: planar cell polarity components with a developing role in cancer.
abstract: Cancers commonly reactivate embryonic developmental pathways to promote the aggressive behavior of their cells, resulting in metastasis and poor patient outcome. While developmental pathways such as canonical Wnt signaling and epithelial-to-mesenchymal transition have received much attention, our understanding of the role of the planar cell polarity (PCP) pathway in tumor progression remains rudimentary. Protein components of PCP, including a subset that overlaps with the canonical Wnt pathway, partition in polarized epithelial cells along the planar axis and are required for the establishment and maintenance of lateral epithelial polarity. Significant insight into PCP regulation of developmental and cellular processes has come from analysis of the functions of the core PCP scaffolding proteins Vangl1 and Vangl2. In particular, studies on zebrafish and with Looptail (Lp) mice, which harbor point mutations in Vangl2 that alter its trafficking and localization, point to roles for the PCP pathway in maintaining cell polarization along both the apical-basal and planar axes as well as in collective cell motility and invasiveness. Recent findings have suggested that the Vangls can promote similar processes in tumor cells. Initial data-mining efforts suggest that VANGL1 and VANGL2 are dysregulated in human cancers, and estrogen receptor (ER)-positive breast cancer patients whose tumors exhibit elevated VANGL1 expression suffer from shortened overall survival. Overall, evidence is beginning to accumulate that the heightened cellular motility and invasiveness associated with PCP reactivation may contribute to the malignancy of some cancer subtypes.
authors: Department of Biochemistry and Molecular MedicineUC Davis School of Medicine, UC Davis Comprehensive Cancer Center, Research Building III, Room 1100B, 4645 2nd Avenue, Sacramento, California 95817, USADepartment of Cell Biology and Human AnatomyUC Davis School of Medicine, Davis, California 95616, USA.
authors: Jason
authors: J
authors: Hatakeyama
authors: Department of Biochemistry and Molecular MedicineUC Davis School of Medicine, UC Davis Comprehensive Cancer Center, Research Building III, Room 1100B, 4645 2nd Avenue, Sacramento, California 95817, USADepartment of Cell Biology and Human AnatomyUC Davis School of Medicine, Davis, California 95616, USA.
authors: Jessica H
authors: JH
authors: Wald
authors: Department of Biochemistry and Molecular MedicineUC Davis School of Medicine, UC Davis Comprehensive Cancer Center, Research Building III, Room 1100B, 4645 2nd Avenue, Sacramento, California 95817, USADepartment of Cell Biology and Human AnatomyUC Davis School of Medicine, Davis, California 95616, USA.
authors: Ignat
authors: I
authors: Printsev
authors: Department of Biochemistry and Molecular MedicineUC Davis School of Medicine, UC Davis Comprehensive Cancer Center, Research Building III, Room 1100B, 4645 2nd Avenue, Sacramento, California 95817, USADepartment of Cell Biology and Human AnatomyUC Davis School of Medicine, Davis, California 95616, USA.
authors: Hsin-Yi Henry
authors: HY
authors: Ho
authors: Department of Biochemistry and Molecular MedicineUC Davis School of Medicine, UC Davis Comprehensive Cancer Center, Research Building III, Room 1100B, 4645 2nd Avenue, Sacramento, California 95817, USADepartment of Cell Biology and Human AnatomyUC Davis School of Medicine, Davis, California 95616, USA klcarraway@ucdavis.edu.
authors: Kermit L
authors: KL
authors: Carraway
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D016764:Cell Polarity; D004847:Epithelial Cells / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C488287:VANGL1 protein, human; C468513:VANGL2 protein, human
keywords: Vangl1; Vangl2; breast cancer; cell migration; developmental pathways; invasiveness; planar cell polarity; polarity