Cadherins: The superfamily critically involved in breast cancer

Maeirah Afzal Ashaie, Ezharul Hoque Chowdhury

Research output: Contribution to journalArticleResearchpeer-review

51 Citations (Scopus)

Abstract

Breast cancer, one of the leading causes of mortality and morbidity among females, is regulated in part by diverse classes of adhesion molecules one of which is known as cadherins. Located at adherens junctions, the members of this super family are responsible for upholding proper cell-cell adhesion. Cadherins possess diverse structures and functions and any alteration in their structures or functions causes impeding of normal mammary cells development and maintenance, thus leading to breast malignancy. E-, N-, P-, VE-, Proto-, desmosomal and FAT cadherins have been found to regulate breast cancer in positive as well as negative fashion, whereby both E-cadherin (CDH1) and N-cadherin (CDH2) contribute significantly towards transitioning from epithelial state to mesenchymal state (EMT) and enacting the abnormal cells to invade and metastasize nearby and distant tissues. Aberration in gene expression of cadherins can be either due to somatic or epigenetic silencing or via transcriptional factors. Besides other cadherins, E-cadherin which serves as hallmark of EMT is associated with several regulatory factors such as Snail, Slug, Twist, Zeb, KLF4, NFI, TBX2, SIX, b-Myb, COX-2, Arf6, FOXA2, GATA3 and SMAR1, which modulate E-cadherin gene transcription to promote or represses tumor invasion and colonization. Signaling molecules such as Notch, TGF-β, estrogen receptors, EGF and Wnt initiate numerous signaling cascades via these vital factors of cell programming, controlling expression of E-cadherin at transcriptional (mRNA) and protein level. Thus, interactions of cadherins with their roles in tumor suppression and oncogenic transformation can be beneficial in providing valuable insights for breast cancer diagnosis and therapeutics development.

Original languageEnglish
Pages (from-to)616-638
Number of pages23
JournalCurrent Pharmaceutical Design
Volume22
Issue number5
DOIs
Publication statusPublished - Feb 2016

Keywords

  • Breast cancer
  • Cadherins
  • CDH1
  • CDH2
  • Cell adhesion
  • EMT
  • Epigenetic silencing
  • Signaling pathways
  • Transcriptional factors
  • Tumor repressor

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