PRMT5 and breast cancer stem cells
Breast cancer stem cells (BCSCs) are a small population of cells within the bulk tumour mass that are considered to be the origin of tumour initiation, contributing to metastatic spread, disease relapse and drug resistance.
Using in vivo mouse models, we have shown that PRMT5 is required for maintaining the BCSC population (Chiang et al., Cell Reports, 2017). Critically, we also demonstrated that if we in vivo depleted PRMT5 after tumour formation, we reduced the number of BCSCs within the tumour, implying that inhibition of PRMT5 could be a way to eradicate chemoresistant BCSCs, preventing disease relapse and increasing patient survival rates.
Mechanistically, we found that one way in which PRMT5 drives breast cancer stem cell function is through the epigenetic regulation of the FOXP1 gene. We are now developing an approached that will enable us to in vivo track BCSCs within a tumour xenograft model to assess the effects of pre-clinical small molecule PRMT5 inhibitors.