IISER Bhopal identifies mechanism behind breast cancer spread

Researchers at the Indian Institute of Science Education and Research (IISER) Bhopal have found the mechanism by which breast cancer cells proliferate and spread.

The findings have important implications in designing of therapeutic interventions for breast cancer as in India, it accounted for 11.1 per cent of cancer deaths in 2020, driving the need for aggressive research to understand and treat this malady.

The study, published in the peer-reviewed journal Oncogenesis, analysed the regulation of a particular gene, called a ESRP1, in breast cancer.

The team found that there is a difference in the expression of the ESRP1 gene between the normal and tumour tissues of breast cancer patients.

The researchers explored the regulatory mechanism behind ESRP1 upregulation in breast tumour tissues.

"Our research, for the first time, shows the reason behind an elevated expression of a key gene, ESRP1, in breast tumour tissue supporting tumour progression," said Dr Sanjeev Shukla, Associate Professor, Department of Biological Sciences at IISER Bhopal.

"Another important part of the discovery was a novel epigenetic regulatory mechanism that governs ESRP1 downregulation in hypoxic tumour tissue, which might help the cancer cells to evade the surrounding tissue and enter the bloodstream," he added.

The team found that in tumour tissues, a transcription factor called E2F1 that regulates transcription of ESRP1 gets upregulated, which increases its expression and eventually leads to excessive growth of breast cancer cells.

Thus, E2F1 could be a molecular drug target to inhibit the growth of both normoxic as well as hypoxic breast cancer cells, Shukla suggested.

"The finding that such intelligent regulatory mechanisms exist in cancer cells to alter the expression of essential genes as and when required, resulting in cancer progression, lays the foundation towards a better understanding of a complex disease and for improved therapeutic strategies," he said.

Further, the team also found the mechanistic aspects of cancer spread to other parts of the body or metastasis.

Cancerous tumours develop regions of reduced oxygen due to poor blood circulation.

It has been known that such oxygen-deprived regions instigate metastasis.

The team showed that it is because E2F1 fails to bind the ESRP1 promoter in oxygen-deprived breast cancer cells, downregulating the expression of ESRP1.

This downregulation causes the cancerous cells to break free from primary cancer and join the bloodstream to be carried to other parts of the body, thereby resulting in metastasis, the researchers explained.

"Our research shows that there is orchestrated activation of ESRP1 in breast cancer, depending on the tumour microenvironment," Shukla noted.