Chronic circadian disruption modulates breast cancer stemness and immune microenvironment to drive metastasis in mice

Eva Hadadi, William Taylor, Xiao-Mei Li, Yetki Aslan, Marthe Villote, Julie Riviere, Gaelle Duvallet, Charlotte Auriau, Sandrine Dulong, Isabelle Raymond-Letron, Sylvain Provot, Annelise Bennaceur-Griscelli, Herve Acloque

Research output: Contribution to journalArticlepeer-review

77 Citations (Scopus)

Abstract

Breast cancer is the most common type of cancer worldwide and one of the major causes of cancer death in women. Epidemiological studies have established a link between night-shift work and increased cancer risk, suggesting that circadian disruption may play a role in carcinogenesis. Here, we aim to shed light on the effect of chronic jetlag (JL) on mammary tumour development. To do this, we use a mouse model of spontaneous mammary tumourigenesis and subject it to chronic circadian disruption. We observe that circadian disruption significantly increases cancer-cell dissemination and lung metastasis. It also enhances the stemness and tumour-initiating potential of tumour cells and creates an immunosuppressive shift in the tumour microenvironment. Finally, our results suggest that the use of a CXCR2 inhibitor could correct the effect of JL on cancer-cell dissemination and metastasis. Altogether, our data provide a conceptual framework to better understand and manage the effects of chronic circadian disruption on breast cancer progression.
Original languageEnglish
Article number3193
JournalNature Communications
Volume11
Issue number1
DOIs
Publication statusPublished - 24 Jun 2020
Externally publishedYes

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