Stem cell discovery highlights importance of DNA methylation in cancer

A study led by Umeå University, Sweden, presents new insights into how stem cells develop and transform into specialized cells. This discovery could lead to a better understanding of how cells divide and grow uncontrollably, leading to the development of cancer.

“The discovery opens a new avenue for future research aimed at developing new, more effective treatments against certain cancers,” says Francesca Aguilo, associate professor at the Department of Molecular Biology at Umeå University and leader of the collaborative study with various institutions, including the University. de Pavia, University of Texas Health Science Center at Houston, Universidad de Extremadura and others.

All cells in the body come from a single fertilized egg. From this single origin, various specialized cells with very different tasks evolve in a process called cellular differentiation. Although all cells share the same origin and share the same genetic information, specialized cells use this information in different ways to perform different functions. This process is regulated by genetic and epigenetic mechanisms.

In the present study, now published in Natural communicationsResearchers studied mouse embryonic stem cells to understand how cells transition from a versatile state to specialized cells.

The LSD1 protein is a key player in this process. It is overexpressed in many cancers and is therefore an important target in cancer treatment research. Several clinical trials aim to inhibit the ability of the LSD1 protein to modify gene expression.

However, the study shows that LSD1 not only affects gene expression in the way previously hypothesized by modifying histones, i.e. the proteins around which the long DNA helices of chromosomes are wound, but that LSD1 also acts as a scaffold, a support structure for other proteins that control DNA methylation.

The researchers were able to see that even when the enzymatic function of LSD1 was inhibited, its supporting capacity could still maintain the DNA methylation patterns necessary for cell differentiation and proliferation. Abnormal DNA methylation is strongly associated with cancer.

The results suggest that for cancer treatments to be effective, it may not be enough to simply block the enzymatic activity of LSD1. Treatments may also need to focus on attacking the supportive role of LSD1.

“So far this is basic research, so there is a long way to go and it is too early to make any promises about new treatments, but this could be an important step for further research into cancer,” Aguilo says.