Posted on Jul 25, 2019, 6 p.m.
A transcription factor called Slug has been found to serve as a command central for determining breast stem cell health that regulates stem cell activity and repair of DNA damage; it likely functions as a safeguard against age related decline of breast stem cell function, according to the researchers.
Slug was previously reported to play a central role in some types of breast cancer, building on their previous work breast cells from humans and mice were used in this study to further explore how Slug may be helpful in maintaining cell fitness.
“These findings help us understand how Slug functions in normal breast tissue and how it may function in breast cancer,” said Charlotte Kuperwasser at Tufts University School of Medicine. “Slug is overexpressed in a subtype of breast cancer called basal-like breast cancer. If Slug is also critical for DNA damage repair mechanisms in basal-like breast cancers, it might increase the attractiveness of Slug as a therapeutic target.”
“Our previous work established that Slug is critical for stem cell activity in breast tissue, but we suspected that there was more to the story,” said Kuperwasser. “In asking what other functions Slug might be performing in breast tissue, particularly with regard to maintaining cell fitness, we found something quite interesting, which is that Slug regulates breast stem cell function partially through DNA damage repair.”
As published in Cell Reports deficiency in human breast cells was found to prevent recruitment of key proteins required for repairing DNA, this function appears to be independent of its role in regulating gene transcription.
While it has not yet been determined whether breast cancer cells utilize Slug’s DNA damage repair function, a connection was made between its multifaceted roles in breast tissue and the biological process of aging in this study.
Aged mice breast tissue was found to have higher levels of DNA damage and lower stem cell activity, these characteristics were also found in Slug deficient breast tissue from young mice; observation of these characters in both models strongly suggests that Slug function is disrupted during aging, and the mechanism of how that function is disrupted is still being investigated.
“Our data point towards Slug acting as a safeguard against breast tissue aging, as it promotes both stem cell activity and efficient DNA damage repair, which are disrupted in aged breast tissue,” said co-first author Kayla Gross.
“But these fountain of youth properties of Slug are certainly a double-edged sword. Breast cancer cells may keep themselves up and running by co-opting the stem cell activity and DNA repair activity of Slug. What will be most important going forward is understanding how Slug is regulated. How do aged cells turn off its functions? How do breast cancer cells turn them on?” continued Gross.
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