IDENTIFICATION OF NICOTINIC ACETYLCHOLINE RECEPTORS REQUIRED FOR BREAST TUMOURIGENESIS

Abstract

Breast cancer continues to be the most common diagnosed cancer among women, and radiation or chemotherapy generally fails to provide durable cure, especially in the context of advanced or metastatic disease. Tumours recurrence is believed to be driven by cancer stem cells, which resist anti-cancer therapy and survive to seed relapse after remission in breast cancer patients. Small molecules inhibitors of nicotinic acetylcholine receptors (nAChR) target cancer stem cells, however, the precise nAChR required for breast cancer stem cell activity is unknown. Hence, we propose to test the capacity of shRNAs that target each individual nAChR to inhibit breast cancer stem cell activity. Briefly, we performed a cancer stem cell based pooled lenti-vector shRNA screen, to identify receptors required for the propagation of breast cancer stem cell enriched cultures. Our results demonstrate that the suppression of multiple receptors can be detected and corresponding genes are essential for TIC viability and survival. We anticipate our approach will identify the relevant nAChR receptor required for breast cancer stem cell activity. Such receptors may represent useful drug targets for the development of anti-breast cancer stem cell therapeutics.