Tamori Shoma, Nozaki Yuka, Motomura Hitomi, Nakane Hiromi, Katayama Reika, Onaga Chotaro, Kikuchi Eriko, Shimada Nami, Suzuki Yuhei, Noike Mei, Hara Yasushi, Sato Keiko, Sato Tsugumichi, Yamamoto Kouji, Hanawa Takehisa, Imai Misa, Abe Ryo, Yoshimori Atsushi, Takasawa Ryoko, Tanuma Sei-Ichi, Akimoto Kazunori
Department of Medicinal and Life Science, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan.
Translational Research Center, Research Institute for Science and Technology, Tokyo University of Science, Chiba, Japan.
Oncotarget. 2018 Nov 23;9(92):36515-36529. doi: 10.18632/oncotarget.26369.
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 ( , = 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 and the cancer stem cell marker . ALDH1 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 cell viability as well as the formation of tumor-spheres by ALDH1 cells. GLO1 knockdown using specific siRNAs also suppressed ALDH1 cell viability, and both TLSC702 and GLO1 siRNA induced apoptosis in ALDH1 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.
乙二醛酶1（GLO1）是一种普遍存在的酶，参与甲基乙二醛的解毒过程，甲基乙二醛是糖酵解的一种细胞毒性副产物，可诱导细胞凋亡。在本研究中，我们发现GLO1基因表达与肿瘤组织学分级相关（ ， = 0.002），且在人基底样乳腺癌组织中升高。约90%的基底样癌为3级肿瘤，同时高表达 和癌症干细胞标志物 。源自MDA - MB 157和MDA - MB 468人基底样乳腺癌细胞系的ALDH1细胞显示出GLO1活性升高。使用TLSC702抑制GLO1可抑制ALDH1细胞活力以及ALDH1细胞形成肿瘤球。使用特异性siRNA敲低GLO1也可抑制ALDH1细胞活力，并且TLSC702和GLO1 siRNA均可诱导ALDH1细胞凋亡。这些结果表明GLO1对ALDH1阳性乳腺癌干细胞的存活至关重要。因此，我们得出结论，GLO1是治疗基底样乳腺癌的一个潜在治疗靶点。
