Glyoxalase 1 gene is highly expressed in basal-like human breast cancers and contributes to survival of ALDH1-positive breast cancer stem cells

// Shoma Tamori 1, 6 , Yuka Nozaki 1, 6 , Hitomi Motomura 1, 6 , Hiromi Nakane 1 , Reika Katayama 1 , Chotaro Onaga 1 , Eriko Kikuchi 1 , Nami Shimada 2 , Yuhei Suzuki 1 , Mei Noike 1 , Yasushi Hara 3 , Keiko Sato 4, 6 , Tsugumichi Sato 2, 6 , Kouji Yamamoto 5, 6 , Takehisa Hanawa 2, 6 , Misa Imai 8, 9 , Ryo Abe 3, 11 , Atsushi Yoshimori 10 , Ryoko Takasawa 2 , Sei-Ichi Tanuma 2, 7 and Kazunori Akimoto 1, 6 1 Department of Medicinal and Life Science, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan 2 Department of Pharmacy, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan 3 Research Institute for Biochemical Sciences, Tokyo University of Science, Chiba, Japan 4 Department of Information Sciences, Faculty of Science and Technology, Tokyo University of Science, Chiba, Japan 5 Department of Biostatistics, Yokohama City University, School of Medicine, Yokohama, Japan 6 Translational Research Center, Research Institute for Science and Technology, Tokyo University of Science, Chiba, Japan 7 Laboratory of Genomic Medicinal Science, Research Institute for Science and Technology, Tokyo University of Science, Chiba, Japan 8 Department of Hematology, Juntendo University School of Medicine, Tokyo, Japan 9 Leading Center for the Development and Research of Cancer Medicine, Juntendo University School of Medicine, Tokyo, Japan 10 Institute for Theoretical Medicine, Inc., Kanagawa, Japan 11 Strategic Innovation and Research Center, Teikyo University, Tokyo, Japan Correspondence to: Kazunori Akimoto, email: akimoto@rs.tus.ac.jp Keywords: cancer stem cell; glyoxalase 1; breast cancer; the Warburg effect; target therapy Received: July 04, 2018 Accepted: November 01, 2018 Published: November 23, 2018 ABSTRACT Glyoxalase 1 (GLO1) is a ubiquitous enzyme involved in the detoxification of methylglyoxal, a cytotoxic byproduct of glycolysis that induces apoptosis. In this study, we found that GLO1 gene expression correlates with neoplasm histologic grade ( χ 2 test , p = 0.002) and is elevated in human basal-like breast cancer tissues. Approximately 90% of basal-like cancers were grade 3 tumors highly expressing both GLO1 and the cancer stem cell marker ALDH1A3 . ALDH1 high cells derived from the MDA-MB 157 and MDA-MB 468 human basal-like breast cancer cell lines showed elevated GLO1 activity. GLO1 inhibition using TLSC702 suppressed ALDH1 high cell viability as well as the formation of tumor-spheres by ALDH1 high cells. GLO1 knockdown using specific siRNAs also suppressed ALDH1 high cell viability, and both TLSC702 and GLO1 siRNA induced apoptosis in ALDH1 high cells. These results suggest GLO1 is essential for the survival of ALDH1-positive breast cancer stem cells. We therefore conclude that GLO1 is a potential therapeutic target for treatment of basal-like breast cancers.