title: Therapeutic targets associated to E-cadherin dysfunction in gastric cancer.
abstract: BACKGROUND
  Epithelial cadherin (E-cadherin) plays a key role in epithelial cell-cell adhesion, contributing to tissue differentiation and homeostasis. Throughout the past decades, research has shed light on the molecular mechanisms underlying E-cadherin's role in tumor progression, namely in invasion and metastization. Emerging evidence established E-cadherin as a tumor suppressor and suggests that targeting E-cadherin or downstream signaling molecules may constitute effective cancer therapeutics.
  
  
  METHODS
  This review aims to cover E-cadherin-mediated signaling during cancer development and progression and highlight putative therapeutic targets.
  
  
  CONCLUSIONS
  Reconstitution of E-cadherin expression or targeting of E-cadherin downstream molecules holds promise in cancer therapies. Considering the high frequency of CDH1 promoter hypermethylation as a second hit in malignant lesions from hereditary diffuse gastric cancer patients, histone deacetylase inhibitors are potential therapeutic agents in combination with conventional chemotherapy, specifically in initial tumor stages. Concerning E-cadherin-mediated signaling, we propose that HER receptors (as epidermal growth factor receptor) and Notch downstream targets are clinically relevant and should be considered in gastric cancer therapeutics and control.
authors: IPATIMUP, Institute of Molecular Pathology and Immunology of the University of Porto , Rua Dr. Roberto Frias s/n, 4200-465 Porto , Portugal +00351 225570700 ; +00351 225570799 ; rseruca@ipatimup.pt carlaol@ipatimup.pt.
authors: Patrícia
authors: P
authors: Carneiro
authors: Joana
authors: J
authors: Figueiredo
authors: Renata
authors: R
authors: Bordeira-Carriço
authors: Maria Sofia
authors: MS
authors: Fernandes
authors: Joana
authors: J
authors: Carvalho
authors: Carla
authors: C
authors: Oliveira
authors: Raquel
authors: R
authors: Seruca
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D006801:Humans; D009361:Neoplasm Invasiveness; D021381:Protein Transport; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D015820:Cadherins