A research team led by Dr. Tapasree Roy Sarkar, Assistant Professor of Biology at Texas A&M University, has uncovered new evidence linking disruptions in the body’s internal clock—known as circadian rhythm disruption (CRD)—to changes in breast tissue and the development of aggressive breast cancer.
Our circadian rhythm governs daily biological processes such as sleep, metabolism, and hormone regulation. When this rhythm is disturbed, as in people who work night shifts or experience irregular sleep patterns, it can have wide-ranging health effects. Epidemiological studies have suggested that women with long-term exposure to shift work face a higher risk of developing breast cancer, but the biological mechanisms behind this connection have remained unclear.
Dr. Sarkar’s lab used a genetically engineered mouse model of aggressive breast cancer to study how chronic CRD affects the mammary gland and tumor progression. Tumor and tissue samples from mice exposed to regular light–dark cycles and those under circadian disruption were analyzed using single-cell RNA sequencing, flow cytometry, multiplex immunostaining, and real-time PCR.
The researchers discovered that prolonged circadian disruption altered normal mammary gland structure, producing abnormal morphological features that may represent early signs of breast cancer. In tumor-bearing mice, CRD significantly increased lung metastasis, altered tumor microenvironment and created an immunosuppressive microenvironment by elevating the expression of a key immune-regulatory protein, LILRB4.
Importantly, when the team applied targeted immunotherapy against LILRB4, they observed a reduction in the CRD-induced immunosuppressive environment and a marked decrease in lung metastasis. Their results also revealed that LILRB4 influences CRD-driven tumor progression through a non-canonical WNT signaling pathway.
Together, these findings identify LILRB4 as a critical molecular link between circadian rhythm disruption and aggressive breast cancer. The study highlights the importance of maintaining healthy daily rhythms and offers new hope for therapies targeting patients whose lifestyles or occupations expose them to irregular light cycles. This work was recently published (https://www.nature.com/articles/s41388-025-03597-5). Dr. Sarkar’s research highlights how environmental and lifestyle factors intersect with molecular biology to shape women’s health, particularly in the context of breast cancer—a central focus of her lab at Texas A&M University.