Interactions between cancer-associated fibroblasts and tumor cells promote MCL-1 dependency in estrogen receptor-positive breast cancers

Kevin Louault; Thomas Bonneaud; Céline Séveno; Patricia Gomez-Bougie; Frédérique Nguyen; Fabien Gautier; Nathalie Bourgeois; Delphine Loussouarn; Olivier Kerdraon; Sophie Barillé-Nion; Pascal Jézéquel; Mario Campone; Martine Amiot; Philippe Juin; Frédérique Souazé

doi:10.1038/s41388-018-0635-z

Journal articles

Interactions between cancer-associated fibroblasts and tumor cells promote MCL-1 dependency in estrogen receptor-positive breast cancers

Kevin Louault ^{1, 2} Thomas Bonneaud ^{1, 2} Céline Séveno ^{1, 2} Patricia Gomez-Bougie ^{3, 2} Frédérique Nguyen ^{1, 4} Fabien Gautier ^{1, 2, 5} Nathalie Bourgeois ^{1, 2} Delphine Loussouarn ⁶ Olivier Kerdraon ^{2, 5} Sophie Barillé-Nion ^{1, 2} Pascal Jézéquel ^{1, 2, 5} Mario Campone ^{1, 2, 5} Martine Amiot ^{3, 2} Philippe Juin ^{1, 2, 5, 7, *} Frédérique Souazé ^{1, 2, 7, *}

* Corresponding author

1 CRCINA-ÉQUIPE 8 - Stress Adaptation and Tumor Escape in Breast Cancer

CRCINA - Centre de Recherche en Cancérologie et Immunologie Nantes-Angers

2 Site de Recherche Intégrée sur le Cancer - SIRIC « ILIAD » [Nantes]

3 CRCINA-ÉQUIPE 10 - Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma

CRCINA - Centre de Recherche en Cancérologie et Immunologie Nantes-Angers

4 Oniris - Atlantic College of Veterinary Medicine, Food Science and Engineering [UNIV Nantes Angers Le Mans]

5 UNICANCER/ICO - Institut de Cancérologie de l'Ouest [Angers/Nantes]

6 Service d’Anatomie et Cytologie Pathologiques [CHU Nantes]

7 CNRS GDR 3697 MicroNiT - Microenvironnement des niches tumorales [UNIV Tours]

Abstract : Selective inhibition of BCL-2 is expected to enhance therapeutic vulnerability in luminal estrogen receptor-positive breast cancers. We show here that the BCL-2 dependency of luminal tumor cells is nevertheless mitigated by breast cancer-associated fibroblasts (bCAFs) in a manner that defines MCL-1 as another critical therapeutic target. bCAFs favor MCL-1 expression and apoptotic resistance in luminal cancer cells in a IL-6 dependent manner while their own, robust, survival also relies on MCL-1. Studies based on ex vivo cultures of human luminal breast cancer tissues further argue that the contribution of stroma-derived signals to MCL-1 expression shapes BCL-2 dependency. Thus, MCL-1 inhibitors are beneficial for targeted apoptosis of breast tumor ecosystems, even in a subtype where MCL-1 dependency is not intrinsically driven by oncogenic pathways.

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Journal articles

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Life Sciences [q-bio] / Cancer

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Submitted on : Wednesday, January 23, 2019 - 4:39:55 PM
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Interactions between cancer-associated fibroblasts and tumor cells promote MCL-1 dependency in estrogen receptor-positive breast cancers

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Interactions between cancer-associated fibroblasts and tumor cells promote MCL-1 dependency in estrogen receptor-positive breast cancers

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