Abstract:

We review the role of cadherins and cadherin-related proteins in human cancer. Cellular and animal models for human cancer are also dealt with whenever appropriate. E-cadherin is the prototype of the large cadherin superfamily and is renowned for its potent malignancy suppressing activity. Different mechanisms for inactivating E-cadherin/CDH1 have been identified in human cancers: inherited and somatic mutations, aberrant protein processing, increased promoter methylation, and induction of transcriptional repressors such as Snail and ZEB family members. The latter induce epithelial mesenchymal transition, which is also associated with induction of "mesenchymal" cadherins, a hallmark of tumor progression. VE-cadherin/CDH5 plays a role in tumor-associated angiogenesis. The atypical T-cadherin/CDH13 is often silenced in cancer cells but up-regulated in tumor vasculature. The review also covers the status of protocadherins and several other cadherin-related molecules in human cancer. Perspectives for emerging cadherin-related anticancer therapies are given.

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Involvement of Members of the Cadherin Superfamily in Cancer

Geert Berx

Frans van Roy

^{Molecular and Cellular Oncology Unit, Department for Molecular Biomedical Research, VIB, Ghent, Belgium}

^{Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium}

^{Molecular Cell Biology Unit, Department for Molecular Biomedical Research, VIB, Ghent, Belgium}

Correspondence:Email: eb.tnegu-biv.rbmd@yornav.f

Abstract

We review the role of cadherins and cadherin-related proteins in human cancer. Cellular and animal models for human cancer are also dealt with whenever appropriate. E-cadherin is the prototype of the large cadherin superfamily and is renowned for its potent malignancy suppressing activity. Different mechanisms for inactivating E-cadherin/CDH1 have been identified in human cancers: inherited and somatic mutations, aberrant protein processing, increased promoter methylation, and induction of transcriptional repressors such as Snail and ZEB family members. The latter induce epithelial mesenchymal transition, which is also associated with induction of “mesenchymal” cadherins, a hallmark of tumor progression. VE-cadherin/CDH5 plays a role in tumor-associated angiogenesis. The atypical T-cadherin/CDH13 is often silenced in cancer cells but up-regulated in tumor vasculature. The review also covers the status of protocadherins and several other cadherin-related molecules in human cancer. Perspectives for emerging cadherin-related anticancer therapies are given.

Abstract

^{BCC, basal cell carcinoma; CRC, colorectal carcinoma; DGC, diffuse gastric carcinoma; HCC, hepatocellular carcinoma; IBC, inflammatory breast carcinoma; ILC, invasive lobular carcinoma; NSCLC, nonsmall cell lung carcinoma; PDAC, pancreatic ductal adenocarcinoma; SCC, squamous cell carcinoma.}

^{NA: not analyzed in this study.}

ACKNOWLEDGMENTS

This research was funded by grants from the FWO, the Geconcerteerde Onderzoeksacties of Ghent University, the Belgian Federation against Cancer, the Association for International Cancer Research (Scotland), and FP7 (TUMIC) of the European Union. We acknowledge Dr. Amin Bredan for critical reading of the manuscript, and the members of our research groups for valuable discussions.

ACKNOWLEDGMENTS

Footnotes

Editors: W. James Nelson and Elaine Fuchs

Additional Perspectives on Cell Junctions available at www.cshperspectives.org

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