Newly discovered gene links stress, irregular body clock to breast cancer

MANILA, Philippines – A newly discovered gene links stress and an irregular body clock to breast cancer, a molecular biologist and her student from the University of the Philippines Diliman (UPD) found in a new study.

Molecular biologist Dr. Pia Bagamasbad and her student, Weand Ybañez, discovered a new gene called Krüppel-like factor 9 (KLF9) in their research paper published on February 23 in the Cancer Cell International journal. This gene functions to suppress tumor growth, and links the effects of stress, regulation of the “light-dark cycle,” and breast cancer.

A disrupted light-dark cycle occurs, for instance, among night shift workers and frequent international travelers.

In their study, based at the UPD-National Institute of Molecular Biology and Biotechnology, the researchers found that KLF9 is downregulated in breast tumors compared to normal breast tissue. This means the gene becomes less responsive due to a decrease in receptors on the cell surface.

Stress hormones regulate KLF9, and the gene oscillates with the 12-hour light-dark cycle, the study found.

The disruption of the circadian cycle is an emerging driver of breast cancer, with epidemiological studies linking shift work and chronic jet lag to risk of the disease, according to the researchers.

In normal body function, the circadian cycle, which involves a regular 24-hour pattern of biological activity, is mainly controlled by the 12-hour light-dark cycle. This regulates several bodily functions, like the sleep-wake cycle, digestion, and the release and suppression of various hormones at certain times of the day.

“In normal breast tissue, the researchers found that KLF9 exhibits a cyclical oscillation pattern indicative of a normally-functioning circadian cycle. However, the regular oscillatory pattern of KLF9 expression is lost in highly aggressive breast cancer,” the UPD College of Science said in a statement on Thursday, March 2.

“Given that KLF9 functions to suppress the growth and spread of breast cancer cells, these findings are the first to provide evidence for KLF9 in the consequential link between stress hormones and alterations in the circadian cycle, such as in lack of sleep, towards breast cancer risk and progression,” the college added.

The researchers said the study highlighted the importance of maintaining a normal circadian cycle, or ensuring a regular body clock. (READ: Prevention-based strategies needed in fight against breast cancer)

“These findings have potential far-reaching implications not just on our understanding of how cancer develops and spreads, and how it can be effectively managed, but more importantly, emphasize the need for policies and interventions that can safeguard the overall health and wellness of women working in industries involving disruption in the regular circadian cycle,” said Bagamasbad.

According to the Global Cancer Observatory (Globocan), breast cancer accounted for 17.7% of new cancer cases in the Philippines in 2020, at 27,163. It is the most common cancer among women, and the third-deadliest cancer among all Globocan’s recorded types behind lung and liver cancer. – Rappler.com