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Transcriptome determinants of lung seeding by mammary tumor cells

ABSTRACT: Transcriptome determinants of lung seeding by mammary tumor cells

PROVIDER: PRJNA412197 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6077110.fastq.gz	Fastqsanger.gz
	SRR6077111.fastq.gz	Fastqsanger.gz
	SRR6077102.fastq.gz	Fastqsanger.gz
	SRR6077112.fastq.gz	Fastqsanger.gz
	SRR6077103.fastq.gz	Fastqsanger.gz

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Transcriptome determinants of lung seeding by mammary tumor cells

Project description: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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