دورية أكاديمية
Stromal NRG1 in luminal breast cancer defines pro-fibrotic and migratory cancer-associated fibroblasts
| العنوان: | Stromal NRG1 in luminal breast cancer defines pro-fibrotic and migratory cancer-associated fibroblasts |
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| المؤلفون: | Berdiel-Acer, Mireia, Maia, Ana, Hristova, Zhivka, Borgoni, Simone, Vetter, Martina, Burmester, Sara, Becki, Corinna, Michels, Birgitta E., Abnaof, Khalid, Binenbaum, Ilona, Bethmann, Daniel, Chatziioannou, Aristotelis, Hasmann, Max, Thomssen, Christoph, Espinet, Elisa, Wiemann, Stefan |
| المصدر: | http://lobid.org/resources/99370678536806441Test#!, 40(15):2651-2666. |
| سنة النشر: | 2021 |
| المجموعة: | Publisso (ZB MED-Publikationsportal Lebenswissenschaften) |
| مصطلحات موضوعية: | Female [MeSH], Proteomics/methods [MeSH], Article, Prognostic markers, Humans [MeSH], Breast Neoplasms/genetics [MeSH], Breast cancer, Neuregulin-1/metabolism [MeSH], Cancer microenvironment, Cancer-Associated Fibroblasts/metabolism [MeSH], Proteomics, Tumor Microenvironment [MeSH] |
| الوصف: | HER3 is highly expressed in luminal breast cancer subtypes. Its activation by NRG1 promotes activation of AKT and ERK1/2, contributing to tumour progression and therapy resistance. HER3-targeting agents that block this activation, are currently under phase 1/2 clinical studies, and although they have shown favorable tolerability, their activity as a single agent has proven to be limited. Here we show that phosphorylation and activation of HER3 in luminal breast cancer cells occurs in a paracrine manner and is mediated by NRG1 expressed by cancer-associated fibroblasts (CAFs). Moreover, we uncover a HER3-independent NRG1 signaling in CAFs that results in the induction of a strong migratory and pro-fibrotic phenotype, describing a subtype of CAFs with elevated expression of NRG1 and an associated transcriptomic profile that determines their functional properties. Finally, we identified Hyaluronan Synthase 2 (HAS2), a targetable molecule strongly correlated with NRG1, as an attractive player supporting NRG1 signaling in CAFs. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://repository.publisso.de/resource/frl:6443702Test; https://doi.org/10.1038/s41388-021-01719-3Test; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049869Test/ |
| DOI: | 10.1038/s41388-021-01719-3 |
| الإتاحة: | https://doi.org/10.1038/s41388-021-01719-3Test https://repository.publisso.de/resource/frl:6443702Test https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049869Test/ |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.B7B59B66 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41388-021-01719-3 |
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