GLO 1 and PKCλ regulate ALDH1-positive breast cancer stem cell survival

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

Research output: Contribution to journalArticlepeer-review

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 ALDH1high cells derived from triple negative breast cancer (TNBC) and basal-like breast cancer were examined. Results: 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. 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.

Original languageEnglish
Pages (from-to)5959-5971
Number of pages13
JournalAnticancer research
Volume41
Issue number12
DOIs
Publication statusPublished - Dec 2021

Keywords

  • ALDH1A3
  • Breast cancer
  • Cancer stem cell
  • GLO 1
  • PKCλ

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