GLO 1 and PKCλ Regulate ALDH1-positive Breast Cancer Stem Cell Survival

Abstract

Background/Aim: We examined the inhibitory effects of both glyoxalase 1 (GLO 1) and protein kinase C (PKC) in aldehyde dehydrogenase 1 (ALDH1)-positive breast cancer stem cells (CSCs). Materials and Methods: Breast cancer genomics datasets (TCGA, n=593; METABRIC, n=1904) were downloaded and statistically analyzed. The effects of GLO 1 and PKC on trypan blue staining and tumor-sphere formation by ALDH1 high cells derived from triple negative breast cancer (TNBC) and basal-like breast cancer were examined. Results: GLO 1 high , PKC high , and ALDH1A3 high tumors were enriched in stage I/II/III/IV samples, associated with the HER2 and TNBC subtypes according to receptor status, and associated with the HER2-enriched and basal-like subtypes according to PAM50. Inhibition of either GLO 1 (TLSC702) or PKC (ANF) suppressed tumor-sphere formation and enhanced death in ALDH1 high cells. TLSC702 also effectively inhibited tumorsphere formation and induced death in PKC knockout ALDH1 high cells. Conclusion: GLO 1 and PKC are important for the survival of ALDH1-positive breast CSCs, and may represent potential therapeutic targets for the treatment of ALDH1-positive breast CSCs.