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Impact of the bone microenvironment on phenotypic plasticity of ER+ breast cancer cells

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE160583 | GEO | 2021/04/16

REPOSITORIES: GEO

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The bone microenvironment increases phenotypic plasticity of ER<sup>+</sup> breast cancer cells.

Project description:Estrogen receptor-positive (ER+) breast cancer exhibits a strong bone tropism in metastasis. How the bone microenvironment (BME) impacts ER signaling and endocrine therapy remains poorly understood. Here, we discover that the osteogenic niche transiently and reversibly reduces ER expression and activities specifically in bone micrometastases (BMMs), leading to endocrine resistance. As BMMs progress, the ER reduction and endocrine resistance may partially recover in cancer cells away from the osteogenic niche, creating phenotypic heterogeneity in macrometastases. Using multiple approaches, including an evolving barcoding strategy, we demonstrated that this process is independent of clonal selection, and represents an EZH2-mediated epigenomic reprogramming. EZH2 drives ER+ BMMs toward a basal and stem-like state. EZH2 inhibition reverses endocrine resistance. These data exemplify how epigenomic adaptation to BME promotes phenotypic plasticity of metastatic seeds, fosters intra-metastatic heterogeneity, and alters therapeutic responses. Our study provides insights into the clinical enigma of ER+ metastatic recurrences despite endocrine therapies.

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Impact of the bone microenvironment on phenotypic plasticity of ER+ breast cancer cells [MCF7]

Project description:Translating Ribosome Affinity Purification (TRAP) sequencing revealed that human osteogenic cells (FOB1.19) strongly alter the transcriptional profile of ER+ breast cancer cells (MCF7) in 3D coculture system.

2021-04-16 | GSE137270 | GEO

Impact of the bone microenvironment on phenotypic plasticity of ER+ breast cancer cells[Osteogenic cells]

Project description:RNA sequencing was used to evaluate the effect of cancer cells on osteogenic cells (FOB 1.19) in presence of estrogen or androgen. Here, we unbiasely evaluated the expression level of fibroblast growth factor receptors (FGFs) in osteogenic cells (FOB) alone.

2021-04-16 | GSE137245 | GEO

Impact of the bone microenvironment on phenotypic plasticity of ER+ breast cancer cells [ATAC-Seq]

Project description:ATAC sequencing was performed to evaluate epigenetic changes induced by the bone microenvironment. We found a global epigenetic reprogramming of ER+ cancer cells deriving from bone which drives stemness and endocrine resistance

2021-04-16 | GSE160582 | GEO

Impact of the bone microenvironment on phenotypic plasticity of ER+ breast cancer cells [Evolving Barcode]

Project description:Evolving barcode was used to evaluate clonal expansion in bone metastases induced by intra-iliac artery injection. The assocoation of these results with ER expression revealed a non-genomic effect of the bone microenvironment on ER heterogeneity.

2021-04-16 | GSE160566 | GEO

Impact of the bone microenvironment on phenotypic plasticity of ER+ breast cancer cells [exome-seq]

Project description:Whole Exome Sequencing (WES) was used to evaluate genomic alterations between parental cells, SCPs (Single Cell-derived Subpopulations) and bone-entrained cells.

2021-04-16 | GSE161181 | GEO

Impact of the bone microenvironment on phenotypic plasticity of ER+ breast cancer cells

Project description:Impact of the bone microenvironment on phenotypic plasticity of ER+ breast cancer cells

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Impact of the bone microenvironment on phenotypic plasticity of ER+ breast cancer cells [MCF7]

Project description:Impact of the bone microenvironment on phenotypic plasticity of ER+ breast cancer cells [MCF7]

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Impact of the bone microenvironment on phenotypic plasticity of ER+ breast cancer cells [Evolving Barcode]

Project description:Impact of the bone microenvironment on phenotypic plasticity of ER+ breast cancer cells [Evolving Barcode]

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Impact of the bone microenvironment on phenotypic plasticity of ER+ breast cancer cells[Osteogenic cells]

Project description:Impact of the bone microenvironment on phenotypic plasticity of ER+ breast cancer cells[Osteogenic cells]