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https://ir.csmu.edu.tw:8080/ir/handle/310902500/23558
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| 题名: | CHPF Regulates the Aggressive Phenotypes of Hepatocellular Carcinoma Cells via the Modulation of the Decorin and TGF-beta Pathways |
| 作者: | Liu, CH;Wu, BR;Ho, YJ;Chu, YH;Hsu, WC;Tseng, TJ;Li, JP;Liao, WC |
| 关键词: | hepatocellular carcinoma;tumor microenvironment;chondroitin polymerizing factor;chondroitin sulfate;decorin |
| 日期: | 2021 |
| 上传时间: | 2022-08-05T09:39:13Z (UTC)
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| 出版者: | MDPI |
| 摘要: | Simple Summary Altered extracellular chondroitin sulfate (CS) contributes to tumor progression in many cancers. CHPF is a key enzyme supporting the elongation of CS. Here we showed that CHPF was frequently downregulated in hepatocellular carcinoma (HCC) tumors compared with adjacent non-tumor tissues, and its downregulation was associated with poor overall survival. CHPF regulated aggressive phenotypes of HCC cells in vitro and in vivo, and the TGF-beta pathway involved in the phenotypical changes. Mechanistically, CHPF modified CS on decorin (DCN), which could facilitate DCN accumulation surrounding HCC cells, and modulate activation of TGF-beta pathway. Indeed, the expression of DCN were positively associated with CHPF levels in primary HCC tissue. The research proposed novel insights into the significance of CHPF, which modified DCN and modulated TGF-beta signaling. Aberrant composition of glycans in the tumor microenvironment (TME) and abnormal expression of extracellular matrix proteins are hallmarks of hepatocellular carcinoma (HCC); however, the mechanisms responsible for establishing the TME remain unclear. We demonstrate that the chondroitin polymerizing factor (CHPF), an enzyme that mediates the elongation of chondroitin sulfate (CS), is a critical elicitor of the malignant characteristics of HCC as it modifies the potent tumor suppressor, decorin (DCN). CHPF expression is frequently downregulated in HCC tumors, which is associated with the poor overall survival of HCC patients. We observed that restoring CHPF expression suppressed HCC cell growth, migration, and invasion in vitro and in vivo. Mechanistic investigations revealed that TGF-beta signaling is associated with CHPF-induced phenotype changes. We found that DCN, as a TGF-beta regulator, is modified by CHPF, and that it affects the distribution of DCN on the surface of HCC cells. Importantly, our results confirm that CHPF and DCN expression levels are positively correlated in primary HCC tissues. Taken together, our results suggest that CHPF dysregulation contributes to the malignancy of HCC cells, and our study provides novel insights into the significance of CS, which affects DCN expression in the TME. |
| URI: | http://dx.doi.org/10.3390/cancers13061261
https://www.webofscience.com/wos/woscc/full-record/WOS:000634359900001
https://ir.csmu.edu.tw:8080/handle/310902500/23558 |
| 關聯: | CANCERS ,2021,v13,issue 6 |
| 显示于类别: | [中山醫學大學研究成果] 期刊論文
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