It has long been recognized that the cell–cell adhesion receptor, E-cadherin, is an important determinant of tumor progression, serving as a suppressor of invasion and metastasis in many contexts. Yet how the loss of E-cadherin function promotes tumor progression is poorly understood. In this review, we focus on three potential underlying mechanisms: the capacity of E-cadherin to regulate β-catenin signaling in the canonical Wnt pathway; its potential to inhibit mitogenic signaling through growth factor receptors and the possible links between cadherins and the molecular determinants of epithelial polarity. Each of these potential mechanisms provides insights into the complexity that is likely responsible for the tumor-suppressive action of E-cadherin.
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We thank our colleagues in our labs for their thoughtful comments and support. AJ and ASY were funded by the National Health and Medical Research Council of Australia, whereas CJG is funded by the NIH (GM076561).
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Jeanes, A., Gottardi, C. & Yap, A. Cadherins and cancer: how does cadherin dysfunction promote tumor progression?. Oncogene 27, 6920–6929 (2008). https://doi.org/10.1038/onc.2008.343
- growth factor receptor
- cell polarity
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