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Stromal NRG1 in luminal breast cancer defines pro-fibrotic and migratory cancer-associated fibroblasts

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Stromal NRG1 in luminal breast cancer defines pro-fibrotic and migratory cancer-associated fibroblasts
Berdiel-Acer, Mireia
Wiemann, Stefan
Maia, Ana
Hristova, Zhivka
Bethmann, Daniel
Abnaof, Khalid
Hasmann, Max
Espinet, Elisa
Burmester, Sara
Vetter, Martina
Becki, Corinna
Borgoni, Simone
Binenbaum, Ilona
Michels, Birgitta
Χατζηιωάννου, Αριστοτέλης
Thomssen, Christoph
Άρθρο σε επιστημονικό περιοδικό
2021-04
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.
Κυτταρολογία (EL)
Βιοχημεία (EL)
Βιοπληροφορική (EL)
Νεοπλάσματα. Όγκοι. Ογκολογία (περ. Καρκίνος, κακινογόνες ουσίες) (EL)
Χημική Βιολογία (EL)
Cytology (EN)
Chemical Biology (EN)
Biochemistry (EN)
Neoplasms. Tumors. Oncology (Incl.cancer, carcinogens) (EN)
Bioinformatics (EN)
Neuregulin-1 (EN)
Humans (EN)
Cancer-Associated Fibroblasts (EN)
Proteomics (EN)
Tumor Microenvironment (EN)
Female (EN)
Breast Neoplasms (EN)
English
Springer Nature
Oncogene
https://creativecommons.org/licenses/by/4.0/deed.el
Copyright © 2021 The Authors
National Hellenic Research Foundation (NHRF)
Helios - Repository of the National Hellenic Research Foundation (NHRF)



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