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

Anticancer research 2021 Dec

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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). 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 ALDH1high cells derived from triple negative breast cancer (TNBC) and basal-like breast cancer were examined. GLO 1high, PKCλhigh, and ALDH1A3high 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 ALDH1high cells. TLSC702 also effectively inhibited tumor-sphere formation and induced death in PKCλ knockout ALDH1high cells. 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. Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Citation

Hitomi Motomura, Shoma Tamori, Masa-Aki Yatani, Ayano Namiki, Chotaro Onaga, Ayaka Ozaki, Ryoko Takasawa, Yasunari Mano, Tsugumichi Sato, Yasushi Hara, Keiko Sato, Yuyun Xiong, Yohsuke Harada, Takehisa Hanawa, Sei-Ichi Tanuma, Kazunori Sasaki, Shigeo Ohno, Kazunori Akimoto. GLO 1 and PKCλ Regulate ALDH1-positive Breast Cancer Stem Cell Survival. Anticancer research. 2021 Dec;41(12):5959-5971