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Archive > Volume 29 Issue 3 > 2022,29(3):209-217. DOI:10.3872/j.issn.1007-385X.2022.03.007 Prev Next
Clinical Research
CTHRC1 promotes the migration and invasion of bladder cancer 5637 cells through activating the FAK-ERK1/2 signaling pathway
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Abstract:
Objective: To investigate the expression of collagen triple helix repeat containing-1 (CTHRC1) in bladder cancer tissues and cells and its effect on the migration and invasion of bladder cancer 5637 cells as well as the related mechanisms. Methods: By referring to the bladder cancer gene expression data in TCGA and Arrayexpress databases, CTHRC1 transcriptional and translational levels were analyzed. 144 cases of bladder cancer tissues and 25 cases of para-cancerous tissues resected in the First Affiliated Hospital of Chongqing Medical University from September 2014 to December 2020 were collected for this study; in addition, human bladder cancer cells (RT4, 5637, T24, UMUC-3 and TCCSUP) and immortalized human ureteral epithelial SV-HUC-1 cells were also collected. The expression levels of CTHRC1 in human bladder cancer tissues and cell lines were detected by immunohistochemistry staining, qPCR and WB. The Kaplan-Meier curve was used to analyze the effect of CTHRC1 expression on overall survival (OS). CTHRC1 expression in 5637 cells was interfered using RNAi technology, and then the effects of CTHRC1 knockdown on migration and invasion of bladder cancer 5637 cells were detected by scratch and Transwell assays. Gene set enrichment analysis (GSEA) was used to predict potential signaling pathways associated with CTHRC1. WB was utilized to detect the effect of CTHRC1 knockdown on the expression of FAK-ERK1/2 pathway related proteins. Results: The transcriptional and translational levels of CTHRC1 were significantly up-regulated in muscle-invasive bladder cancer tissues and cells (all P<0.05), and the 5-year OS was significantly shorter in the patients with high CTHRC1 expression as compared with those with low expression (P<0.05). The migration and invasion of bladder cancer 5637 cells were reduced following CTHRC1 knockdown (all P<0.01). GSEA showed that the CTHRC1 high-expression group was mainly enriched in focal adhesion kinase (FAK), regulation of actin cytoskeleton, and FAK-ERK1/2 signaling pathways. WB assay showed that recombinant CTHRC1 protein promoted the activation of FAK-ERK1/2 signaling pathway in bladder cancer 5637 cells (P<0.05 or P<0.01). Conclusion: CTHRC1 expression is up-regulated in invasive bladder cancer and closely related to the poor prognosis of bladder cancer patients. CTHRC1 enhances the invasion and metastasis of bladder cancer cells, which may be associated with the activation of the FAK-ERK1/2 signaling pathway.
Keywords:
collagen triple helix repeat containing-1 (CTHRC1) ; bladder cancer ; 5637 cell ; migration ; invasion ; FAK-ERK1/2 signaling pathway ; prognosis
Clc Number:
R737.14; R730.23; R730.7
