| Added by | pcoopman |
|---|---|
| Group name | EquipePC |
| Item Type | Journal Article |
| Title | The Syk Kinase Promotes Mammary Epithelial Integrity and Inhibits Breast Cancer Invasion by Stabilizing the E-Cadherin/Catenin Complex |
| Creator | Kassouf et al. |
| Author | Toufic Kassouf |
| Author | Romain Maxime Larive |
| Author | Anne Morel |
| Author | Serge Urbach |
| Author | Nadir Bettache |
| Author | Ma Cleofas Marcial Medina |
| Author | Fabrice Mèrezègue |
| Author | Gilles Freiss |
| Author | Marion Peter |
| Author | Florence Boissière-Michot |
| Author | Jérôme Solassol |
| Author | Philippe Montcourrier |
| Author | Peter Coopman |
| Abstract | 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 ?-, ?-, 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-cadherin/catenin complex with zonula occludens proteins and the actin cytoskeleton. Conditional Syk knockout in the lactating mouse mammary gland perturbed alveologenesis and disrupted E-cadherin localization at adherens junctions, corroborating the observations in cells. Hence, Syk is involved in the maintenance of the epithelial integrity of the mammary gland via the phosphorylation and stabilization of the E-cadherin/catenin adherens junction complex, thereby inhibiting cell migration and malignant tumor invasion. |
| Publication | Cancers |
| Volume | 11 |
| Issue | 12 |
| Date | Dec 07, 2019 |
| Journal Abbr | Cancers (Basel) |
| Language | eng |
| DOI | 10.3390/cancers11121974 |
| ISSN | 2072-6694 |
| Library Catalog | PubMed |
| Extra | PMID: 31817924 |
| Tags | breast cancer, E-cadherin, first-last-corresponding, intercellular adhesion, original, protein tyrosine kinase, top, tumor invasion, tumor suppressor |
| Date Added | 2019/12/13 - 14:33:00 |
| Date Modified | 2019/12/13 - 14:33:00 |
| Notes and Attachments | PubMed entry (Attachment) Texte intégral (Attachment) |
Institut de Recherche en Cancérologie de
