CD44-mediated activation of α5β1-integrin, cortactin and paxillin signaling underpins adhesion of basal-like breast cancer cells to endothelium and Fibronectin-enriched matrices
| Autor: | Cheryl McFarlane, Nicola Montgomery, David Waugh, A. D. K. Hill, Suzanne McFarlane |
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| Přispěvatelé: | McFarlane, Suzanne, McFarlane, Cheryl, Montgomery, Nicola, Hill, Ashleigh, Waugh, David JJ |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Pathology
medicine.medical_specialty integrin Integrin Breast Neoplasms Extracellular matrix breast cancer fibronectin Cell Line Tumor medicine Cell Adhesion Humans CD44 Cell adhesion Fibronectin Paxillin biology Adhesion Cell biology Fibronectins Hyaluronan Receptors Oncology Cancer cell biology.protein Female vascular endothelium Cortactin Research Paper Integrin alpha5beta1 Signal Transduction |
| Zdroj: | Oncotarget McFarlane, S, McFarlane, C, Montgomery, N, Hill, A & Waugh, D J J 2015, ' CD44-Mediated Activaton of α5β1-Intergrin, Cortactin and Paxillin Signaling Underpins Ashesion of basal-like breat cancer cells to Endotherlium and Fibronectin-enriched Matrices ', Oncotarget, vol. 6, no. 34, pp. 36762-36773 . https://doi.org/10.18632/oncotarget.5461 |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.5461 |
| Popis: | CD44 expression is elevated in basal-like breast cancer (BLBC) tissue, and correlates with increased efficiency of distant metastasis in patients and experimental models. We sought to characterize mechanisms underpinning CD44-promoted adhesion of BLBC cells to vascular endothelial monolayers and extracellular matrix (ECM) substrates. Stimulation with hyaluronan (HA), the native ligand for CD44, increased expression and activation of β1-integrin receptors, and increased α5-integrin subunit expression. Adhesion assays confirmed that CD44-signalling potentiated BLBC cell adhesion to endothelium and Fibronectin in an α5B1-integrin-dependent mechanism. Co-immunoprecipitation experiments confirmed HA-promoted association of CD44 with talin and the β1-integrin chain in BLBC cells. Knockdown of talin inhibited CD44 complexing with β1-integrin and repressed HA-induced, CD44-mediated activation of β1-integrin receptors. Immunoblotting confirmed that HA induced rapid phosphorylation of cortactin and paxillin, through a CD44-dependent and β1-integrin-dependent mechanism. Knockdown of CD44, cortactin or paxillin independently attenuated the adhesion of BL-BCa cells to endothelial monolayers and Fibronectin. Accordingly, we conclude that CD44 induced, integrin-mediated signaling not only underpins efficient adhesion of BLBC cells to BMECs to facilitate extravasation but initiates their adhesion to Fibronectin, enabling penetrant cancer cells to adhere more efficiently to underlying Fibronectin-enriched matrix present within the metastatic niche. Refereed/Peer-reviewed |
| Databáze: | OpenAIRE |
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