Title:Cadherins: The Superfamily Critically Involved in Breast Cancer
VOLUME: 22 ISSUE: 5
Author(s):Maeirah Afzal Ashaie and Ezharul Hoque Chowdhury
Affiliation:Faculty of Medicine, Nursing and Health Sciences, Monash University, Australia.
Keywords:Breast cancer, cell adhesion, cadherins, CDH1, CDH2, epigenetic silencing, EMT, tumor repressor, transcriptional factors,
signaling pathways.
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 superfamily 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 Ecadherin
(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.
