HISTOLOGY AND HISTOPATHOLOGY

From Cell Biology to Tissue Engineering

 

Review

Cadherins down-regulation: towards a better understanding of their relevance in colorectal cancer

Lorena Losi1, Tommaso Zanocco-Marani1 and Alexis Grande2

1Department of Life Sciences and 2Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy

Offprint requests to: Lorena Losi, Department of Life Sciences, Unit of Pathology, Via del Pozzo 71, 41124 Modena, Italy. e-mail: lorena.losi@unimore.it


Summary. The down-regulation of cadherin expression in colorectal cancer (CRC) has been widely studied. However, existing data on cadherin expression are highly variable and its relevance to CRC development has not been completely established. This review examines published studies on cadherins whose down-regulation has been already demonstrated in CRC, trying to establish a relationship with promoter methylation, the capacity to influence the Wnt / CTNNB1 (catenin beta 1, beta-catenin) signaling pathway and the clinical implications for disease outcome. Moreover, it also analyses factors that may explain data variability and highlights the importance of considering the altered subcellular localization of the examined cadherins. The results of this survey reveal that thirty of one hundred existing cadherins appear to be down-regulated in CRC. Among these, ten are cadherins, sixteen are protocadherins, equally divided between clustered and non clustered, and four are cadherin - related. These findings suggest that, to better define the role played by cadherin down-regulation in CRC pathogenesis, the expression of multiple rather than individual cadherins should be taken into account and further functional studies are necessary to clarify the relative ability of individual cadherins to inhibit CTNNB1 therefore acting as tumor suppressors. Histol Histopathol 35, 1391-1402 (2020)

Key words: Cadherins, Wnt / CTNNB1 signaling, CDH1, Protocadherin, Cadherin-related protein

DOI: 10.14670/HH-18-236