breast cancerResearchers have discovered a small RNA molecule that helps maintain the activity in both healthy and cancerous breast tissues. The study, scheduled to be published in next month’s issue of Nature Cell Biology, discusses how the “microRNA” promotes deadly forms of breast cancer with the effects potentially improving the efficacy of existing breast cancer therapies.

A number of tumours contain “cancer stem cells” that can drive formation. However, some tumours, including triple negative breast cancers, are specifically deadly as they contain large numbers of cancer stem cells that self- renew and resist differentiation.  The microRNA protects breast cancer stem cells from the effects of interferon’s secreted by immune cells present in the tumour.

Yibin Kang, the Warner Lambert/Parke-Davis Professor of Molecular Biology, and his colleagues looked for short RNA molecules called microRNAs that can bind and inhibit protein coding messenger RNAs to reduce the levels of specific proteins. The researchers found one microRNA, called miR-199a, which aids MaSCs retain their stem cell activity by suppressing the production of a protein called LCOR, which binds DNA to regulate gene expression. The team showed that when they boosted miR-199a levels in mouse MaSCs, they suppressed LCOR and increased normal stem cell function. Equally, when they increased LCOR levels, they could curtail mammary gland stem cell activity.

Michael Clarke, the Karel H. and Avice N. Beekhuis professor in cancer biology at Stanford School of Medicine, Institute of Stem Cell Biology and Regenerative Medicine, explained, “This is a very nice study linking a normal and malignant mammary gland stem cell program to protection from immune modulators. It clearly has therapeutic implications for designing strategies to rationally target the breast cancer stem cells with immune modulators.”

Toni Celià -Terrassa, an associate research scholar in the Kang lab and the first author of the study, added, “This study unveils a new property of breast cancer stem cells that give them advantages in their interactions with the immune system, and therefore it represents an excellent opportunity to exploit for improving immunotherapy of cancer.”

Stem cells give rise to the different cell types in adult tissues but, in order to maintain these tissues throughout adulthood, stem cells must retain their activity for decades. They do this by “self-renewing”, dividing to form additional stem cells, and resisting the effects of environmental signals that would otherwise cause them to prematurely differentiate into other cell types.

Kang commented, “Interferons have been widely used for the treatment of multiple cancer types. These treatments might become more effective if the interferon-resistant cancer stem cells can be rendered sensitive by targeting the miR-199a-LCOR pathway.”