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The bone microenvironment increases phenotypic plasticity of ER + breast cancer cells - PubMed

The bone microenvironment increases phenotypic plasticity of ER + breast cancer cells - PubMed

Source :

https://pubmed.ncbi.nlm.nih.gov/33878299/

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 expressi ...

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    Key Points
    • Estrogen receptor-positive (ER+) breast cancer has a propensity to metastasize to bone, however the means by which the bone microenvironment (BME) affects ER signaling and endocrine therapy needs to be better elucidated.
    • In the current study, researchers identified various pathways that are changed in cancer cells by the bone microenvironment (BME).
    • They found that the osteogenic niche transiently and reversibly decreases ER expression and activities characteristic of bone micrometastases (BMMs), thus resulting in endocrine resistance.
    • “As BMMs progress,” the authors wrote, “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.”
    • According to the authors, study data demonstrates “how epigenomic adaptation to BME promotes phenotypic plasticity of metastatic seeds, fosters intra-metastatic heterogeneity, and alters therapeutic responses.” Moreover, the study elucidates ER+ metastatic recurrences regardless of endocrine therapies.