<p>Extracellular matrix protein 1 (ECM1) is associated with carcinogenesis potential of human bladder cancer</p>

Abstract

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.

Gene Expression Profiles Identified Novel Urine Biomarkers for Diagnosis and Prognosis of High-Grade Bladder Urothelial Carcinoma

“…Previous investigation identified that upregulated ECM1 is associated with BC growth, migration, apoptosis and postoperative recurrence, which was in agreement with our results (25). However, the biological function of ECM1 in different tumors remains controversial.…”

“…However, the biological function of ECM1 in different tumors remains controversial. Wang' s study indicated that ECM1 might enhance cell proliferation and invasiveness by regulating the expression of glucose transporter 1, lactate dehydrogenase and hypoxia-inducible factor 1α (25). There is also evidence that ECM1 potentiates the phosphorylation of epidermal growth factor receptor (EGFR) and extracellular signal-regulated kinase through physical interaction with EGFR and activation of EGFR signaling in breast cancer development (26).…”

TERT Promoter Mutations and Their Impact on Gene Expression Profile in Papillary Thyroid Carcinoma

“…Extracellular matrix protein 1 (ECM1), in turn, is a glycoprotein involved in cell proliferation, angiogenesis, migration, and metastases. Its elevated expression was observed in several malignancies, including thyroid, gastric, colorectal, lung carcinoma, invasive ductal breast carcinomas, hepatocellular cancer, and others [ 44 , 45 ]. A significantly high increase in ECM1 expression was observed in malignant epithelial tumors, especially in these tumors with distant metastases [ 44 ].…”

MiR-486-3p inhibits the proliferation, migration and invasion of retinoblastoma cells by targeting ECM1

“…ECM1 was as a 'biological glue' binding to components of the dermal-epidermal junction in the framework of normal skin [41]. ECM1 was first found in osteoblasts stromal cells, and high ECM1 levels were subsequently detected in bladder cancer [42], thyroid cancer [43] and other malignant tumors [44]. Chen et al [45] showed that ECM1 was highly expressed in hepatocellular carcinoma specimens, and could promote the migration and invasion of HCC cells.…”