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

Anticancer Res. 2021 Dec;41(12):5959-5971. doi: 10.21873/anticanres.15415.

ABSTRACT

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^high cells derived from triple negative breast cancer (TNBC) and basal-like breast cancer were examined.

RESULTS: GLO 1^high, PKCλ^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 PKCλ (ANF) suppressed tumor-sphere formation and enhanced death in ALDH1^high cells. TLSC702 also effectively inhibited tumor-sphere formation and induced death in PKCλ knockout ALDH1^high 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.

PMID:34848450 | DOI:10.21873/anticanres.15415