Vangl1 and Vangl2: Planar cell polarity components with a developing role in cancer

Jason Hatakeyama, Jessica H. Wald, Ignat Printsev, Hsin-Yi Henry Ho, Kermit L Carraway

Research output: Contribution to journalArticle

29 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)345-356
Number of pages12
JournalEndocrine-Related Cancer
Volume21
Issue number5
DOIs
StatePublished - Oct 1 2014

Fingerprint

Cell Polarity
Cellular Structures
Neoplasms
Wnt Signaling Pathway
Epithelial-Mesenchymal Transition
Data Mining
Zebrafish
Point Mutation
Estrogen Receptors
Cell Movement
Proteins
Epithelial Cells
Maintenance
Breast Neoplasms
Neoplasm Metastasis
Survival

Keywords

  • Breast cancer
  • Cell migration
  • Developmental pathways
  • Invasiveness
  • Planar cell polarity
  • Polarity
  • Vangl1
  • Vangl2

ASJC Scopus subject areas

  • Endocrinology
  • Oncology
  • Cancer Research
  • Endocrinology, Diabetes and Metabolism

Cite this

Vangl1 and Vangl2 : Planar cell polarity components with a developing role in cancer. / Hatakeyama, Jason; Wald, Jessica H.; Printsev, Ignat; Ho, Hsin-Yi Henry; Carraway, Kermit L.

In: Endocrine-Related Cancer, Vol. 21, No. 5, 01.10.2014, p. 345-356.

Research output: Contribution to journalArticle

Hatakeyama, Jason ; Wald, Jessica H. ; Printsev, Ignat ; Ho, Hsin-Yi Henry ; Carraway, Kermit L. / Vangl1 and Vangl2 : Planar cell polarity components with a developing role in cancer. In: Endocrine-Related Cancer. 2014 ; Vol. 21, No. 5. pp. 345-356.
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