Glyoxalase 1 gene is highly expressed in basal-like human breast cancers and contributes to survival of ALDH1-positive breast cancer stem cells
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Shoma Tamori1,6, Yuka Nozaki1,6, Hitomi Motomura1,6, Hiromi Nakane1, Reika Katayama1, Chotaro Onaga1, Eriko Kikuchi1, Nami Shimada2, Yuhei Suzuki1, Mei Noike1, Yasushi Hara3, Keiko Sato4,6, Tsugumichi Sato2,6, Kouji Yamamoto5,6, Takehisa Hanawa2,6, Misa Imai8,9, Ryo Abe3,11, Atsushi Yoshimori10, Ryoko Takasawa2, Sei-Ichi Tanuma2,7 and Kazunori Akimoto1,6
1Department of Medicinal and Life Science, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan
2Department of Pharmacy, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan
3Research Institute for Biochemical Sciences, Tokyo University of Science, Chiba, Japan
4Department of Information Sciences, Faculty of Science and Technology, Tokyo University of Science, Chiba, Japan
5Department of Biostatistics, Yokohama City University, School of Medicine, Yokohama, Japan
6Translational Research Center, Research Institute for Science and Technology, Tokyo University of Science, Chiba, Japan
7Laboratory of Genomic Medicinal Science, Research Institute for Science and Technology, Tokyo University of Science, Chiba, Japan
8Department of Hematology, Juntendo University School of Medicine, Tokyo, Japan
9Leading Center for the Development and Research of Cancer Medicine, Juntendo University School of Medicine, Tokyo, Japan
10Institute for Theoretical Medicine, Inc., Kanagawa, Japan
11Strategic Innovation and Research Center, Teikyo University, Tokyo, Japan
Kazunori Akimoto, email: [email protected]
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
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 (χ2 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. ALDH1high 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 ALDH1high cell viability as well as the formation of tumor-spheres by ALDH1high cells. GLO1 knockdown using specific siRNAs also suppressed ALDH1high cell viability, and both TLSC702 and GLO1 siRNA induced apoptosis in ALDH1high 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.
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