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

Breast cancer is the most common type and one of the major causes of cancer death in woman worldwide. Epidemiological studies have established a link between night shift work and increased cancer risk, suggesting that circadian disruption may interfere with carcinogenesis. We aim to shed light on the effect of chronic jetlag on mammary tumour development. Therefore, we used a mouse model of spontaneous mammary tumorigenesis that we exposed to chronic circadian disruption. We observed that circadian disruption significantly increases cancer cell dissemination and metastasis. It also enhances the stemness and tumour–initiating potential of tumour cells and creates an immunosuppressive shift in the tumour microenvironment. We finally showed that all these defects can be corrected by the use of a CXCR2 inhibitor. Altogether, our data provide a conceptual framework to better understand and manage the effects of chronic circadian disruption on breast cancer progression.