CDH11 contributes to bladder cancer progression via regulation of mitochondrial energy metabolism.
Patients with advanced bladder cancer (BC) have a poor prognosis and limited treatment options. Therefore, we searched for potential new therapeutic targets using existing big data. First, we collected gene expression datasets of BC cell lines from the Gene Expression Omnibus (GEO) and extracted genes that were highly expressed in advanced BC cell lines. We also extracted genes highly expressed in advanced BC patients from The Cancer Genome Atlas (TCGA). We performed an integrated analysis of these genes to identify genes involved in BC progression, combined with Kaplan-Meier analysis, and identified CDH11 as an involved gene in bladder cancer progression. CDH11 knockdown (KD) cells were established using shRNA against UM-UC-3, an advanced BC cell line. While CDH11 KD did not alter cell proliferation, invasion nor migration in vitro, CDH11 KD significantly suppressed tumor growth in in vivo subcutaneous xenograft mice model. RNA-seq revealed that CDH11 KD cells decreased the expression of genes related to mitochondrial metabolism, and in fact, a flux analyzer revealed decreased mitochondrial activity in the KD cell line. Furthermore, the experiments using CDH11 inhibitor also showed a decrease in mitochondrial activity in vitro, and inhibition of tumor growth in vivo as well as knockdown experiments. These results suggest that CDH11 is involved in BC progression and is a potential therapeutic target. Overall design: To investigate the role of CDH11 in bladder cancer (UM-UC-3), CDH11 was knocked down using shRNA.