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GLO 1 and PKCλ Regulate ALDH1-positive Breast Cancer Stem Cell Survival. | LitMetric
Background/aim : We examined the inhibitory effects of both glyoxalase 1 (GLO 1) and protein kinase C (PKC)λ 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 PKCλ on trypan blue staining and tumor-sphere formation by ALDH1 cells derived from triple negative breast cancer (TNBC) and basal-like breast cancer were examined.Results : GLO 1, PKCλ, and ALDH1A3 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 PKCλ (ANF) suppressed tumor-sphere formation and enhanced death in ALDH1 cells. TLSC702 also effectively inhibited tumor-sphere formation and induced death in PKCλ knockout ALDH1 cells.Conclusion : GLO 1 and PKCλ are important for the survival of ALDH1-positive breast CSCs, and may represent potential therapeutic targets for the treatment of ALDH1-positive breast CSCs.
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