Dysadherin: A Novel Oncogenic Molecular Biomarker in Oesophageal Cancer

Abstract

Dysadherin or FXYD5 is a transmembrane glycoprotein, identified for the first time
in 2002 by a team of Japanese researchers.1 Although, it is generally accepted that most of its
action is derived from the increased maximal velocity (Vmax) of the Na+-K+-ATPase that promotes,
there are several actions of dysadherin that cannot be attributed to its interaction with
the Na+-K+-ATPase.2 Dysadherin is a well-described cancer-associated protein and a potential
oncogenic molecular target with promising future significances. It has been distinctly shown, in
both the cases of in vivo and in vitro studies, that when expressed in malignant tumours, it signifies
augmented tumorigenesis with enhanced metastatic potential and haematogenous spread
and is thus linked to poor prognosis.3,4 On the contrary, studies based on human cancer cell
lines have demonstrated that introduction of small interfering RNA (siRNA) against dysadherin
leads to downregulation and subsequent membranous underexpression of dysadherin, instigating
accordingly decreased collective and individual cell motility with subsequent inhibition of
tumour aggressiveness and metastatic potential.5 Its main interaction in carcinogenesis takes
place with E-cadherin (epithelial cadherin); the most important adhesion molecules of the cadherin
family. E-cadherin is involved in cancer development in more than 90% of human cancers,
as most are carcinomas of epithelial origin. E-cadherin mediates homophilic cell-to-cell
adhesion and promotes adherence between neighboring epithelial cells; its decreased cellular
expression is hence associated with enhanced disconnection and dispersal of epithelial cells,
promoting cell detachment from the primary lesion and consequently exhibiting increased metastatic
potential.