Number of the records: 1
Transcription factor c-Myb inhibits breast cancer lung metastasis by suppression of tumor cell seeding
- 1.0488378 - BFÚ 2018 RIV GB eng J - Journal Article
Knopfová, L. - Biglieri, E. - Volodko, N. - Masařík, M. - Hermanová, M. - Garzon, J.F.G. - Ducka, M. - Kučírková, T. - Souček, Karel - Šmarda, J. - Beneš, P. - Borsig, L.
Transcription factor c-Myb inhibits breast cancer lung metastasis by suppression of tumor cell seeding.
Oncogene. Roč. 37, č. 8 (2018), s. 1020-1030. ISSN 0950-9232. E-ISSN 1476-5594
Institutional support: RVO:68081707
Keywords : inflammatory chemokines * colorectal-carcinoma * gene
OECD category: Biochemistry and molecular biology
Impact factor: 6.634, year: 2018
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.
Permanent Link: http://hdl.handle.net/11104/0282968
Number of the records: 1