The role of c-Myb in site-selective metastases of breast tumors: the focus on the tumor-endothelial cell interactions
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| Year of publication | 2013 |
| Type | Conference abstract |
| MU Faculty or unit | |
| Citation | |
| Description | Deregulation of the c-Myb transcription factor, the stem/progenitor cell regulator, occurs frequently in breast cancer and other malignancies. Both tumorogenic and tumor suppressive effects of c-Myb have been reported in breast tumors. We described previously that the Myb-overexpressing 4T1 mammary tumors in syngeneic BALB/c model rarely metastasized to lungs in contrast to control tumors, though the formation of the bone and liver metastases was not affected. We hypothesized that the selective disadvantage of these cells in lung colonization might result from their inability to penetrate a vessel wall and underlying basement membrane in lung parenchyma. In this study, we investigated the MYB function in tumor-endothelial cell interactions including adhesion, intercalation and polarisation, with particular focus on the regulation of actin cytoskeleton dynamics. We demonstrated that (1) the MYB-overexpressing MDA-MB-231 breast cancer cells lost capacity of transendothelial migration., (2) ectopically expressed c-Myb did not affect adhesion rate of breast carcinoma MDA-MB-231 cells to endothelial cell monolayer, (3) c-Myb downregulated expression of moesin, the ERM protein, and interstitial collagenase, The gene expression profiles available for human breast carcinomas confirmed this observation. Differential regulation of cytoskeleton dynamics by control of ERM proteins and suppression of interstitial collagenase may contribute to the damaged extravasation and site-selective metastases of the MYB-overepressing breast tumors. |
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