Chronic Circadian Disruption Modulates Breast Cancer Stemness and Immune Microenvironment to Drive Metastasis in Mice

Overview

Journal Nat Commun

Specialty Biology

Date 2020 Jun 26

PMID 32581213

Citations 84

Authors

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

Affiliations

Soon will be listed here.

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.

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