Lineage plasticity enables cancer cells to evolve and become resistant to chemotherapy. It’s important for the development of a type of triple-negative breast cancer called basal-like breast cancer (BLBC). Scientists know that BLBC arises when luminal cells in the breast reprogram and develop into more primitive basal-like cells. But the underlying mechanisms are not well understood.

In research published online on June 9 in Cell Reports, researchers led by Wenjun Guo, Ph.D., associate professor of cell biology and a member of the Gottesman Institute for Stem Cell Biology and Regenerative Medicine at Einstein identified a key stem cell program that promotes cell plasticity and cancer progression in BLBC. The researchers found that mammary stem cell factor SOX9 is essential for driving luminal cells to develop into basal-like cells during BLBC formation. The researchers also showed that SOX9 plays a crucial role in causing benign tumor lesions to progress to invasive carcinoma.

These findings may lead to better drugs for preventing and treating BLBC, an aggressive cancer that has no effective therapy and disproportionally affects younger women and women of African and Hispanic descent.