Scientists have discovered a protein that begins producing milk after breastfeeding ends – something that could provide effective new targets for cancer therapies.
The groundbreaking study from the University of Sheffield has uncovered a protein called Rac1, which acts as a crucial switch to kick-start milk production in breast cells when lactation stops and the breasts are already beginning to return to their pre-pregnancy state.
Once babies begin eating solids, the breasts reduce milk production and undergo a contraction to return to activity. The milk-producing units are disassembled through cellular suicide to remove redundant tissue. During intermittent feeding, the retracted breast can noticeably reflex to re-initiate feeding if feeding is resumed. Until now it was not known how this process took place.
Dr Nasreen Akhtar and her team, from the University of Sheffield’s Department of Oncology and Metabolism, investigated the mammary glands of mice – which are structurally similar to humans. They discovered that when Rac1 is present, cell death occurs along with autophagy – a process in which cells begin to eat their own parts in a desperate attempt to stay alive.
Most importantly, the study published in the journal Biology PLUSrevealed that half-dead, half-live cells infected with autophagy can be brought back to life to resume milk production, when lactating, but cells without the Rac1 protein cannot.
This finding could provide new insights into how breast cancer cells acquire resistance to cell death in non-permissive environments.
Lead author Dr Nasreen Akhtar, Lecturer in Developmental Cell Biology at the University of Sheffield, said: “Rac1 not only causes living breast cells to devour their dying neighbours, but is also responsible for the cells eating themselves.
“The influx of milk caused by lactation is thought to initiate lactation, but what happens at the cellular level has puzzled scientists for years.
“Despite the massive wave of cell death that occurs in the first phase of the end of lactation, if breastfeeding resumes, the breast can reverse the process and re-lactate. This is an unsafe built-in mechanism to prevent the breast from drying out too quickly.”
“They are particularly important in nature for the survival of mammals, for example, if a lactating mammal is separated from its young for longer than expected while foraging, it will still be able to feed once they are reunited.
“It is remarkable that some mammals have a really long reversible phase; for example, the Cape fur seal that goes on long foraging trips, for up to 28 days can still return lactate once it resumes feeding on shore.”
Dr. Akhtar explained why this study could have important implications for targeting cancer cells that are resistant to current therapies.
She added: “The risk of breast cancer is higher in the post-conception years – possibly due to altered activity during the post-weaning remodeling phase.
“The discovery here can reveal potential pathways and proteins that cancer cells exploit for survival and growth.”
Mironov, A.; et al. (2023) Rac1 controls cell turnover and reversal of docking in mammary glands after birth. Biology PLUS. doi.org/10.1371/journal.pbio.3001583.