Beyond N-Cadherin, Relevance of Cadherins 5, 6 and 17 in Cancer Progression and Metastasis
Department of Molecular Biomedicine, Centro de Investigaciones Biológicas (CIB)-Consejo Superior de Investigaciones Científicas (CSIC), Ramiro de Maeztu 9, 28039 Madrid, Spain
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(13), 3373; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20133373
Received: 30 May 2019 / Revised: 1 July 2019 / Accepted: 6 July 2019 / Published: 9 July 2019
(This article belongs to the Special Issue Activations of Cadherin Signaling in Cancer)
Cell-cell adhesion molecules (cadherins) and cell-extracellular matrix adhesion proteins (integrins) play a critical role in the regulation of cancer invasion and metastasis. Although significant progress has been made in the characterization of multiple members of the cadherin superfamily, most of the published work continues to focus in the switch E-/N-cadherin and its role in the epithelial–mesenchymal transition. Here, we will discuss the structural and functional properties of a subset of cadherins (cadherin 17, cadherin 5 and cadherin 6) that have an RGD motif in the extracellular domains. This RGD motif is critical for the interaction with α2β1 integrin and posterior integrin pathway activation in cancer metastatic cells. However, other signaling pathways seem to be affected by RGD cadherin interactions, as will be discussed. The range of solid tumors with overexpression or “de novo” expression of one or more of these three cadherins is very wide (gastrointestinal, gynaecological and melanoma, among others), underscoring the relevance of these cadherins in cancer metastasis. Finally, we will discuss different evidences that support the therapeutic use of these cadherins by blocking their capacity to work as integrin ligands in order to develop new cures for metastatic patients.