Transcription factor c-Myb inhibits breast cancer lung metastasis by suppression of tumor cell seeding
Jazyk angličtina Země Velká Británie, Anglie Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
Grantová podpora
152361
Swiss National Science Foundation - Switzerland
152901
Swiss National Science Foundation - Switzerland
PubMed
29084208
PubMed Central
PMC6711763
DOI
10.1038/onc.2017.392
PII: onc2017392
Knihovny.cz E-zdroje
- MeSH
- apoptóza MeSH
- chemokin CCL2 genetika metabolismus MeSH
- lidé MeSH
- lokální recidiva nádoru genetika metabolismus patologie MeSH
- myši inbrední BALB C MeSH
- myši inbrední C57BL MeSH
- myši inbrední NOD MeSH
- myši SCID MeSH
- myši MeSH
- nádorové biomarkery genetika metabolismus MeSH
- nádorové buňky kultivované MeSH
- nádorové mikroprostředí MeSH
- nádory plic genetika metabolismus sekundární MeSH
- nádory prsu genetika metabolismus patologie MeSH
- prognóza MeSH
- proliferace buněk MeSH
- protoonkogenní proteiny c-myb genetika metabolismus MeSH
- regulace genové exprese u nádorů * MeSH
- xenogenní modely - testy protinádorové aktivity MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- CCL2 protein, human MeSH Prohlížeč
- chemokin CCL2 MeSH
- nádorové biomarkery MeSH
- protoonkogenní proteiny c-myb MeSH
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.
Department of Experimental Biology Faculty of Science Masaryk University Brno Czech Republic
Institute of Biophysics of the Czech Academy of Sciences Brno Czech Republic
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