Background: Bladder cancer (BCa) is a common urological malignant tumor worldwide, and recurrence and death still remain high. New therapeutic targets are needed to treat patients who are not sensitive to current therapy. Extracellular matrix protein 1 (ECM1) is a key player in multiple epithelial malignancies. However, the knowledge regarding the expression of ECM1 in BCa and the mechanisms by which ECM1 affects BCa tumor progression is unclear.
Materials and methods: ECM1 expression levels in BCa tissues and cells were detected by quantitative real-time PCR (qRT-PCR), immunohistochemistry and Western blot. ECM1 expression was suppressed by shRNAs. Cell Counting Kit-8 (CCK-8), luminescent cell viability assay and 5-ethynyl-2'-deoxyuridine (EdU) assay were used to detect cell proliferation. Flow cytometry and transwell assay were used to evaluate cell apoptosis and invasion, respectively. All statistical analyses were performed by using the GraphPad Prism 7 software package.
Results: In this study, the expression of ECM1  in BCa specimens and cell lines was examined and displayed a significant increase compared with noncancerous counterparts, while ECM1 -knockdown affected not only cell proliferation and migration, but also cell invasion ability and apoptosis potential, corresponding to the finding that ECM1  overexpression in BCa patients was associated with a poor prognosis. Additionally, after suppression of ECM1 , the expression of glucose transporter 1 (GLUT1 ), lactate dehydrogenase (LDHA ) and hypoxia-inducible factor 1α (HIF-1α ), genes involved in Warburg effect regulation, were significantly decreased, and the lactate production was also obviously reduced in ECM1 -silenced cells.
Conclusion: Our investigations revealed that the expression of ECM1 was closely associated with tumor cell growth, migration and apoptosis at least in part through regulation of Warburg effect, defining ECM1 as an effective predictor in the carcinogenesis and postoperative recurrence of human BCa.
Keywords: bladder cancer, extracellular matrix protein 1, proliferation, migration, invasion