Glyoxalase 1 and protein kinase Cλ as potential therapeutic targets for late-stage breast cancer

Hitomi Motomura, Ayaka Ozaki, Shoma Tamori, Chotaro Onaga, Yuka Nozaki, Yuko Waki, Ryoko Takasawa, Kazumi Yoshizawa, Yasunari Mano, Tsugumichi Sato, Kazunori Sasaki, Hitoshi Ishiguro, Yohei Miyagi, Yoji Nagashima, Kouji Yamamoto, Keiko Sato, Takehisa Hanawa, Sei Ichi Tanuma, Shigeo Ohno, Kazunori Akimoto

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Cancer cells upregulate the expression levels of glyco- lytic enzymes in order to reach the increased glycolysis required. One such upregulated glycolytic enzyme is glyoxalase 1 (GLO 1), which catalyzes the conversion of toxic methylglyoxal to nontoxic S-D-lactoylglutathione. Protein kinase Cλ (PKCλ) is also upregulated in various types of cancer and is involved in cancer progression. In the present study, the association between enhanced glycolysis and PKCλ in breast cancer was investigated. In human breast cancer, high GLO 1 expression was associated with high PKCλ expression at the protein (P<0.01) and mRNA levels (P<0.01). Furthermore, Wilcoxon and Cox regression model analysis revealed that patients with stage III-IV tumors with high GLO 1 and PKCλ expression had poor overall survival compared with patients expressing lower levels of these genes [P=0.040 (Gehan-Breslow generalized Wilcoxon test) and P=0.031 (hazard ratio, 2.36; 95% confidence interval, 1.08-5.16), respectively]. Treatment of MDA-MB-157 and MDA-MB-468 human basal-like breast cancer cells with TLSC702 (a GLO 1 inhibitor) and/or aurothiomalate (a PKCλ inhibitor) reduced both cell viability and tumor-sphere formation. These results suggested that GLO 1 and PKCλ were cooperatively involved in cancer progression and contributed to a poor prognosis in breast cancer. In conclusion, GLO 1 and PKCλ serve as potentially effective therapeutic targets for treatment of late-stage human breast cancer.

Original languageEnglish
Article number547
JournalOncology Letters
Volume22
Issue number1
DOIs
Publication statusPublished - Jul 2021

Keywords

  • Breast cancer
  • Glyoxalase 1
  • Immunohistochemistry
  • Protein kinase Cλ

Fingerprint

Dive into the research topics of 'Glyoxalase 1 and protein kinase Cλ as potential therapeutic targets for late-stage breast cancer'. Together they form a unique fingerprint.

Cite this