Cancers, Vol. 11, Pages 1974: The Syk Kinase Promotes Mammary Epithelial Integrity and Inhibits Breast Cancer Invasion by Stabilizing the E-Cadherin/Catenin Complex

Cancers, Vol. 11, Pages 1974: The Syk Kinase Promotes Mammary Epithelial Integrity and Inhibits Breast Cancer Invasion by Stabilizing the E-Cadherin/Catenin Complex Cancers doi: 10.3390/cancers11121974 Authors: Toufic Kassouf Romain Maxime Larive Anne Morel Serge Urbach Nadir Bettache Ma Cleofas Marcial Medina Fabrice Mèrezègue Gilles Freiss Marion Peter Florence Boissière-Michot Jérôme Solassol Philippe Montcourrier Peter Coopman While first discovered in immunoreceptor signaling, the Syk protein kinase behaves as a tumor and metastasis suppressor in epithelial cells. Its reduced expression in breast and other carcinomas is correlated with decreased survival and increased metastasis risk, but its action mechanism remains largely unknown. Using phosphoproteomics we found that Syk phosphorylated E-cadherin and α-, β-, and p120-catenins on multiple tyrosine residues that concentrate at intercellular junctions. Increased Syk expression and activation enhanced E-cadherin/catenin phosphorylation, promoting their association and complex stability. In human breast cancer cells, Syk stimulated intercellular aggregation, E-cadherin recruitment and retention at adherens junctions, and promoted epithelial integrity, whereas it inhibited cell migration and invasion. Opposite effects were obtained with Syk knockdown or non-phosphorylatable mutant E-cadherin expression. Mechanistically, Syk stimulated the interaction of the E-...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research