Informace o publikaci
Transcription factor c-Myb inhibits breast cancer lung metastasis by suppression of tumor cell seeding
| Autoři | |
|---|---|
| Rok publikování | 2018 |
| Druh | Článek v odborném periodiku |
| Časopis / Zdroj | Oncogene |
| Fakulta / Pracoviště MU | |
| Citace | |
| Doi | http://dx.doi.org/10.1038/onc.2017.392 |
| Obor | Genetika a molekulární biologie |
| Klíčová slova | Myb; endothelium; inflammation; Ccl2; metastasis; breast cancer |
| Popis | Metastasis accounts for most of cancer-related deaths. Paracrine signaling between tumor cells and the stroma induces changes in the tumor microenvironment required for metastasis. Transcription factor c-Myb was associated with breast cancer (BC) progression but its role in metastasis remains unclear. Here we show that increased c-Myb expression in BC cells inhibits spontaneous lung metastasis through impaired tumor cell extravasation. On contrary, BC cells with increased lung metastatic capacity exhibited low c-Myb levels. We identified a specific inflammatory signature, including Ccl2 chemokine; that was expressed in lung metastatic cells but was suppressed in tumor cells with higher c-Myb levels. Tumor cell-derived Ccl2 expression facilitated lung metastasis and rescued trans-endothelial migration of c-Myb overexpressing cells. Clinical data show that the identified inflammatory signature, together with a MYB expression, predicts lung metastasis relapse in BC patients. These results demonstrate that the c-Myb-regulated transcriptional program in BCs results in a blunted inflammatory response and consequently suppresses lung metastasis. |
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