150th Anniversary Series: Desmosomes and the Hallmarks of Cancer

Abstract

Desmosomes represent adhesive, spot-like intercellular junctions that in association with intermediate filaments mechanically link neighboring cells and stabilize tissue architecture. In addition to this structural function, desmosomes also act as signaling platforms involved in the regulation of cell proliferation, differentiation, migration, morphogenesis, and apoptosis. Thus, deregulation of desmosomal proteins has to be considered to contribute to tumorigenesis. Proteolytic fragmentation and downregulation of desmosomal cadherins and plaque proteins by transcriptional or epigenetic mechanisms were observed in different cancer entities suggesting a tumor-suppressive role. However, discrepant data in the literature indicate that context-dependent differences based on alternative intracellular, signal transduction lead to altered outcome. Here, modulation of Wnt/β-catenin signaling by plakoglobin or desmoplakin and of epidermal growth factor receptor signaling appears to be of special relevance. This review summarizes current evidence on how desmosomal proteins participate in carcinogenesis, and depicts the molecular mechanisms involved.

Keywords::

• cell–cell contacts
• desmosomes
• adherens junctions
• plakoglobin
• plakophilin
• desmoplakin
• cancer

ACKNOWLEDGEMENT

The authors apologize to all colleagues whose work we did not discuss or cite in this manuscript. We thank Dr. Laura Bloch for critical reading of the manuscript.

Declaration of interest: The authors declare no conflict of interest. The authors alone are responsible for the content and writing of the paper.