MCT1 regulates aggressive and metabolic phenotypes in bladder cancer

Background: Monocarboxylate transporter isoform 1 (MCT1) is an important molecule in mediating lactate transportation. Recent studies have shown an oncogenic role of MCT1 in cancer development. Methods: In this study, we aimed to investigate the expression and role of MCT1 in bladder cancer (BCa). MCT1 expression was detected in 124 BCa tissues and their clinicopathological significance was analyzed. We also used The Cancer Genome Atlas database to explore the prognostic association of MCT1 with BCa. Cell proliferation, migration and invasion assays were performed on BCa cells in which MCT1 was downregulated. The effect of MCT1 on BCa cell aerobic glycolysis, as well as its association with HIF-1α, was tested. Results: We found that high MCT1 expression correlated with lymph node and distant metastasis. Patients with high-MCT1 expression showed shorter overall survival than those with low-MCT1 expression. Knockdown of MCT1 inhibited BCa cell proliferation, migration and invasion, and affected expression of epithelial-mesenchymal transition related proteins. Downregulation of MCT1 decreased lactate levels in cell medium, as well as HK2, GLUT1 and LDHB expression. In addition, MCT1 expression was partly dependent on HIF-1α. Conclusions: Taken together, our study has shown a prognostic role of MCT1 in BCa, and provided potential diagnostic and therapeutic options for BCa patients.

Journal of Cancer. 2018 Jun 15*** epublish ***

Guiming Zhang, Yongjian Zhang, Dahai Dong, Fangming Wang, Xiaocheng Ma, Fengju Guan, Lijiang Sun

Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, China.