A new study has found that the transcription factor Slug acts as “command central” for determining breast stem-cell health, regulating stem cell activity and the repair of DNA damage. In addition, Slug likely safeguards against age-related decline of breast stem-cell function.
Transcription factors are proteins that bind to DNA sequences, and play a role in cancer. The research team previously reported that Slug has a central role in some types of breast cancers. Building on their prior work, the researchers used both human and mouse breast cells to examine how Slug might help maintain cell fitness.
Slug is overexpressed in a subtype of breast cancer called basal-like breast cancer. If it also proves critical for DNA damage-repair mechanisms in basal-like breast cancers, say the researchers, Slug’s attractiveness as a therapeutic target may increase.
Stem cells’ main function is to replenish tissues, for which they must remain healthy. One way they do this is by efficiently repairing damaged DNA, as unrepaired damage can cause mutations that disrupt normal stem cell behavior. If they detect DNA damage, stem cells activate checkpoints to prevent damaged cells from replicating, and they only regain regenerative activity after the damaged DNA has been properly repaired.
While exploring other functions that Slug might be performing in breast tissue, the researchers found that Slug deficiency in human breast cells prevented the recruitment of key proteins that are essential for DNA repair. Apparently, this function of Slug is independent of its role in regulating gene transcription.
The researchers still need to determine whether breast cancer cells utilize Slug's DNA damage repair function, but the current study did make a connection between the protein’s various roles in breast tissue and aging.
As stem cells age, they are less able to replicate and repair DNA damage. The breast tissue from aged mice was found to have higher levels of DNA damage and lower stem cell activity. Importantly, these characteristics were also found in Slug-deficient breast tissue from young mice. This observation strongly suggests that Slug function is disrupted during aging. The precise mechanism for how this occurs is still being investigated by the researchers.
Source: MedicalXpress, July 16, 2019