Meyer, Stefanie and Orso, Evelyn and Schmitz, Gerd and Landthaler, Michael and Vogt, Thomas (2007) Lubrol-RAFTs in melanoma cells: A molecular platform for tumor-promoting ephrin-B2-integrin-beta 1 interaction. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 127 (7). pp. 1615-1621. ISSN 0022-202X,
Full text not available from this repository. (Request a copy)Abstract
Ephrins control cell motility and matrix adhesion. These functions play a pivotal role in cancer progression, for example, in malignant melanomas. We have previously shown that the ephrin-B2-tumor-promoting action is partly mediated by integrin-beta 1 interaction. However, the subcellular prerequisites for molecular interaction like molecular proximity and co-compartmentalization have not been elucidated yet. Specific cholesterol-rich microdomains, termed lipid rafts (RAFTS), are known to be essential for functional ephrin-B2 signalling and integrin-mediated effects. Therefore, we addressed the question whether RAFT co-compartmentalization of both molecules could provide the molecular platform for their tumor-promoting interaction. In this study, we show that overexpressed ephrin-B2 is not only compartmentalized to classical Triton X-100 RAFTs in B16 melanoma cells, but also to the recently defined Lubrol-RAFTs. Interestingly, in the melanoma cells investigated, integrin-JA is also preferentially detected in such Lubrol-RAFTs. Accordingly, the presence of ephrin-B2 and integrin-beta 1 in RAFTs and their function in cell migration and matrix attachment are highly sensitive to RAFT disruption by cholesterol depletion. Confocal fluorescence microscopy analyses also support the concept of a close molecular proximity and functional interplay of ephrin-B2 and integrin-B1 in the plasma membrane. We conclude that Lubrol-RAFTs probably represent the platform for tumor-promoting ephrin-B2-integrin-B1 interaction, which could become an interesting target for future antitumoral therapies.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | LIPID RAFTS; CANCER CELLS; EPHRINB LIGANDS; MEMBRANE; ADHESION; MICRODOMAINS; REVERSE; OVEREXPRESSION; RECEPTORS; PROTEINS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Dermatologie und Venerologie Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 02 Dec 2020 12:20 |
| Last Modified: | 02 Dec 2020 12:20 |
| URI: | https://pred.uni-regensburg.de/id/eprint/32558 |
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