Transcription factor c-Myb inhibits breast cancer lung metastasis by suppression of tumor cell seeding

KNOPFOVÁ, Lucia, Elisabetta BIGLIERI, Natalya VOLODKO, Michal MASAŘÍK, Markéta HERMANOVÁ, Jesus Francisco GLAUS GARZÓN, Monika DÚCKA, Tereza KUČÍRKOVÁ, Karel SOUČEK, Jan ŠMARDA, Petr BENEŠ and Lubor BORSIG. Transcription factor c-Myb inhibits breast cancer lung metastasis by suppression of tumor cell seeding. Oncogene. London: Nature Publishing Group, 2018, vol. 37, No 8, p. 1020-1030. ISSN 0950-9232. Available from: https://dx.doi.org/10.1038/onc.2017.392.

Basic information

• Original name: Transcription factor c-Myb inhibits breast cancer lung metastasis by suppression of tumor cell seeding
• Authors: KNOPFOVÁ, Lucia (203 Czech Republic, guarantor, belonging to the institution), Elisabetta BIGLIERI (380 Italy), Natalya VOLODKO (804 Ukraine), Michal MASAŘÍK (203 Czech Republic, belonging to the institution), Markéta HERMANOVÁ (203 Czech Republic, belonging to the institution), Jesus Francisco GLAUS GARZÓN (756 Switzerland), Monika DÚCKA (703 Slovakia, belonging to the institution), Tereza KUČÍRKOVÁ (203 Czech Republic, belonging to the institution), Karel SOUČEK (203 Czech Republic, belonging to the institution), Jan ŠMARDA (203 Czech Republic, belonging to the institution), Petr BENEŠ (203 Czech Republic, belonging to the institution) and Lubor BORSIG (703 Slovakia).
• Edition: Oncogene, London, Nature Publishing Group, 2018, 0950-9232.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 10601 Cell biology
• Country of publisher: United Kingdom of Great Britain and Northern Ireland
• Confidentiality degree: is not subject to a state or trade secret
• WWW: URL
• Impact factor: Impact factor: 6.634
• RIV identification code: RIV/00216224:14310/18:00100761
• Organization unit: Faculty of Science
• Doi: http://dx.doi.org/10.1038/onc.2017.392
• UT WoS: 000425905700005
• Keywords (in Czech): Myb; endotel; zánět; Ccl2; metastáza; prsní nádory
• Keywords in English: Myb; endothelium; inflammation; Ccl2; metastasis; breast cancer
• Tags: 14110112, 14110515, 14110518, NZ, podil
• Tags: International impact, Reviewed

Abstract

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.

Links

• GJ17-08985Y, research and development project: Name: Prozánětlivá signalizace pod kontrolou proteinu c-Myb v bazálních prsních karcinomech

Investor: Czech Science Foundation

• IZ73Z0_152361/1, interní kód MU: Name: c-Myb and Ruk/CIN85 modulate the signaling in breast cancer thereby affecting metastasis (Acronym: c-Myb and Ruk/CIN85 signaling affects metastasis)

Investor: Ostatní - foreign, SCOPES - Scientific Co-operation between Eastern Europe and Switzerland