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Cell density, Her2 and progesterone signaling regulate dissemination of breast cancer cells [miRNA-Seq]

ABSTRACT: Disseminated breast cancer cells display genotypes disparate from the predominant clone of the primary tumor before manifestation of metastasis, suggesting that cancer cell dissemination occurs preferentially early; however, the underlying molecular mechanisms are unknown. Investigating metastasis in a Her2-driven mouse model, we found that the progesterone-induced paracrine cytokines Wnt4 and Rankl induced migration and early dissemination shortly after Her2 activation. Once tumorigenic growth was established, progesterone receptor (PgR) expression was lost and Wnt4/Rankl induced proliferation. The altered response from migration to proliferation was determined by cell density involving miRNA-regulated PgR expression and was reversible. Cells from early, low-density lesions displayed more functional stemness traits than cells from dense, advanced tumors, migrated more and founded significantly more metastases. The data suggest that many metastases are derived from early-disseminated cancer cells, implying that our concepts for systemic therapy need to be revised.

ORGANISM(S): Mus musculus

PROVIDER: GSE68682 | GEO | 2016/12/08

SECONDARY ACCESSION(S): PRJNA283389

REPOSITORIES: GEO

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Cell density, Her2 and progesterone signaling regulate dissemination of breast cancer cells [Gene expression]

Project description:Disseminated breast cancer cells display genotypes disparate from the predominant clone of the primary tumor before manifestation of metastasis, suggesting that cancer cell dissemination occurs preferentially early; however, the underlying molecular mechanisms are unknown. Investigating metastasis in a Her2-driven mouse model, we found that the progesterone-induced paracrine cytokines Wnt4 and Rankl induced migration and early dissemination shortly after Her2 activation. Once tumorigenic growth was established, progesterone receptor (PgR) expression was lost and Wnt4/Rankl induced proliferation. The altered response from migration to proliferation was determined by cell density involving miRNA-regulated PgR expression and was reversible. Cells from early, low-density lesions displayed more functional stemness traits than cells from dense, advanced tumors, migrated more and founded significantly more metastases. The data suggest that many metastases are derived from early-disseminated cancer cells, implying that our concepts for systemic therapy need to be revised.

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Cell density, Her2 and progesterone signaling regulate dissemination of breast cancer cells

Project description:Cell density, Her2 and progesterone signaling regulate dissemination of breast cancer cells

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Mus musculus

Project description:Cell density, Her2 and progesterone signaling regulate dissemination of breast cancer cells [Gene expression]

| PRJNA283390 | ENA

Mus musculus

Project description:Cell density, Her2 and progesterone signaling regulate dissemination of breast cancer cells [miRNA-Seq]

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