Academic Journal
Dual role for miR-34a in the control of early progenitor proliferation and commitment in the mammary gland and in breast cancer
| العنوان: | Dual role for miR-34a in the control of early progenitor proliferation and commitment in the mammary gland and in breast cancer |
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| المؤلفون: | Bonetti P., Climent M., Panebianco F., Tordonato C., Santoro A., Marzi M. J., Pelicci P. G., Ventura A., Nicassio F. |
| المساهمون: | P. Bonetti, M. Climent, F. Panebianco, C. Tordonato, A. Santoro, M.J. Marzi, P.G. Pelicci, A. Ventura, F. Nicassio |
| بيانات النشر: | Nature Publishing Group |
| سنة النشر: | 2019 |
| المجموعة: | The University of Milan: Archivio Istituzionale della Ricerca (AIR) |
| مصطلحات موضوعية: | Animal, Breast Neoplasm, Cell Differentiation, Cell Line, Tumor, Cell Proliferation, Cell Self Renewal, Epithelial Cell, Female, Human, Mammary Glands, Mesenchymal Stem Cell, Mice, Knockout, MicroRNA, Neoplastic Stem Cell, RNA, Neoplasm, Spheroids, Cellular, Triple Negative Breast Neoplasm, Wnt Signaling Pathway, Settore MED/04 - Patologia Generale, Settore MED/06 - Oncologia Medica |
| الوصف: | The role of the tumour-suppressor miR-34 family in breast physiology and in mammary stem cells (MaSCs) is largely unknown. Here, we revealed that miR-34 family, and miR-34a in particular, is implicated in mammary epithelium homoeostasis. Expression of miR-34a occurs upon luminal commitment and differentiation and serves to inhibit the expansion of the pool of MaSCs and early progenitor cells, likely in a p53-independent fashion. Mutant mice (miR34-KO) and loss-of-function approaches revealed two separate functions of miR-34a, controlling both proliferation and fate commitment in mammary progenitors by modulating several pathways involved in epithelial cell plasticity and luminal-to-basal conversion. In particular, miR-34a acts as endogenous inhibitor of the Wnt/beta-catenin signalling pathway, targeting up to nine upstream regulators at the same time, thus modulating the expansion of the MaSCs/early progenitor pool. These multiple roles of miR-34a are maintained in a model of human breast cancer, in which chronic expression of miR-34a in triple-negative mesenchymal-like cells (enriched in cancer stem cells—CSCs) could promote a luminal-like differentiation programme, restrict the CSC pool, and inhibit tumour propagation. Hence, activation of miR-34a-dependent programmes could provide a therapeutic opportunity for the subset of breast cancers, which are rich in CSCs and respond poorly to conventional therapies. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/30093634; info:eu-repo/semantics/altIdentifier/wos/WOS:000455851200005; volume:38; issue:3; firstpage:360; lastpage:374; numberofpages:15; journal:ONCOGENE; http://hdl.handle.net/2434/656656; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85052526547 |
| DOI: | 10.1038/s41388-018-0445-3 |
| الاتاحة: | http://hdl.handle.net/2434/656656 https://doi.org/10.1038/s41388-018-0445-3 |
| رقم الانضمام: | edsbas.BEF9BB0F |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41388-018-0445-3 |
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