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p120-catenin in cancer - mechanisms, models and opportunities for intervention.

Authors
  • Schackmann, Ron C J1
  • Tenhagen, Milou
  • van de Ven, Robert A H
  • Derksen, Patrick W B
  • 1 Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands. , (Netherlands)
Type
Published Article
Journal
Journal of Cell Science
Publisher
The Company of Biologists
Publication Date
Aug 15, 2013
Volume
126
Issue
Pt 16
Pages
3515–3525
Identifiers
DOI: 10.1242/jcs.134411
PMID: 23950111
Source
Medline
Keywords
License
Unknown

Abstract

The epithelial adherens junction is an E-cadherin-based complex that controls tissue integrity and is stabilized at the plasma membrane by p120-catenin (p120, also known as CTNND1). Mutational and epigenetic inactivation of E-cadherin has been strongly implicated in the development and progression of cancer. In this setting, p120 translocates to the cytosol where it exerts oncogenic properties through aberrant regulation of Rho GTPases, growth factor receptor signaling and derepression of Kaiso (also known as ZBTB33) target genes. In contrast, indirect inactivation of the adherens junction through conditional knockout of p120 in mice was recently linked to tumor formation, indicating that p120 can also function as a tumor suppressor. Supporting these opposing functions are findings in human cancer, which show that either loss or cytoplasmic localization of p120 is a common feature in the progression of several types of carcinoma. Underlying this dual biological phenomenon might be the context-dependent regulation of Rho GTPases in the cytosol and the derepression of Kaiso target genes. Here, we discuss past and present findings that implicate p120 in the regulation of cancer progression and highlight opportunities for clinical intervention.

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