Studies on cancer stem cells give new insights into breast cancer progression and potential therapies

Cancer stem cells (CSCs) are proposed to initiate cancer and promote metastasis. I will present our data identifying the CSC marker, aldehyde dehydrogenase 1A3 (ALDH1A3). Furthermore, we have shown that ALDH1A3 is more than just a marker for CSCs and actively contributes to triple-negative breast cancer (TNBC) progression by producing retinoic acid (RA). RA is a cell-signaling and transcription-inducing molecule which mediates important cellular processes such as proliferation, cell cycle arrest, apoptosis and differentiation. Intriguingly, the effects of ALDH1A3 and RA on breast tumor progression can be either promoting or inhibiting, depending on the molecular subtype of the TNBC (i.e. promoting in mesenchymal-like subtypes and inhibiting in basal-like subtypes). Our results suggest that, depending on the TNBC molecular subtype, patients may benefit from RA-based or anti-RA based therapies (e.g. citral). Finally, using RNAi genome-wide screening strategies we have identified potential novel effectors of the RA signaling pathway which mediate ALDH1A3/RA-induced tumor progression or inhibition. In summary, our work on CSCs has led to new insights regarding both the signaling pathways determining breast cancer progression, and the identification of novel druggable targets.