Journal
ONCOGENE
Volume 37, Issue 8, Pages 1020-1030Publisher
SPRINGERNATURE
DOI: 10.1038/onc.2017.392
Keywords
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Funding
- SCOPES/SNF [IZ73Z0-152361]
- Czech Science Foundation [17-08985Y]
- National Program of Sustainability II [LQ1605-MEYS CR]
- ICRC-ERA-HumanBridge [316345]
- Grant Agency of Masaryk University [MUNI/0877/2016]
- SNF [310030-152901]
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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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