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TGF-β1 Promotes Hepatocellular Carcinoma Invasion and Metastasis via ERK Pathway-Mediated FGFR4 Expression

机译:TGF-β1通过ERK途径介导的FGFR4表达促进肝癌的侵袭和转移

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Background/Aims TGF-β1 is beneficial during early liver disease but is tumor-progressive during late stages especially for hepatocellular carcinoma (HCC). Thus, exploring the underlying mechanisms may provide information about a potentially therapeutic role of TGF-β1 in HCC. Methods Western blot and real-time quantitative PCR were used to quantify FGFR4 expression in HCC cell lines and a normal liver cell line. After constructing the best silencing FGFR4 expression vector, migration and invasiveness of TGF-β1 in HCC was studied in vitro and in vivo. Western blot was used to study the mechanism of TGF-β1 induction on FGFR4 expression with various inhibitors. Results HepG2 cell lines had the most FGFR4 expression, and data show that silencing FGFR4 suppressed cell proliferation, invasion and migration in HCC induced by TGF-β1 in vitro and in vivo. Moreover, TGF-β1 induced FGFR4 expression through the ERK pathway. Conclusion Promoting FGFR4 expression via the ERK pathway, TGF-β1 contributes to HCC invasion and metastasis.
机译:背景/目的TGF-β1在早期肝脏疾病中有益,但在晚期尤其是肝细胞癌(HCC)时具有肿瘤进展性。因此,探索潜在的机制可能提供有关TGF-β1在HCC中潜在治疗作用的信息。方法采用Western blot和实时定量PCR分别检测HCC细胞和正常肝细胞中FGFR4的表达。在构建了最佳沉默的FGFR4表达载体后,我们在体内外研究了TGF-β1在肝癌中的迁移和侵袭性。用Western blot研究了各种抑制剂对TGF-β1诱导FGFR4表达的作用机制。结果HepG2细胞株中FGFR4的表达最多,数据表明FGFR4沉默可抑制TGF-β1诱导的HCC细胞增殖,侵袭和迁移。此外,TGF-β1通过ERK途径诱导FGFR4表达。结论TGF-β1通过ERK途径促进FGFR4表达,促进肝癌的侵袭和转移。

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