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

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 (<i>χ</i> ² <i>test</i>, <i>p</i> = 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 <i>GLO1</i> and the cancer stem cell marker <i>ALDH1A3</i>. 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.