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Knockdown of HIP1 expression promotes ligand-induced endocytosis of EGFR in HeLa cells

机译:抑制HIP1表达促进HeLa细胞中配体诱导的EGFR内吞

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摘要

Huntington-interacting protein 1 (HIP1) is associated with various tumor types; however, its precise functions in tumor cells are unclear. In this study, the effects of HIP1 on the degradation of EGFR, which have important roles in carcinogenesis after EGF stimulation, were examined. After screening 17 cell lines, the coexpression of HIP1 and EGFR was detected in HeLa cells. Accordingly, the expression of HIP1 was knocked down in HeLa cells using various HIP1 siRNA sequences. The endocytosis of EGFR and localization of clathrin in HeLa cells were examined after stimulation by EGF at various concentrations (i.e., 1.5 and 100 ng/ml). After HIP1 expression was blocked by siRNAs, EGFR endocytosis was accelerated and this effect was dependent on the EGF concentration. This endocytosis was colocalized with clathrin expression. These findings indicate that the inhibition of HIP1 can accelerate the endocytosis and degradation of EGFR. Furthermore, they suggest that HIP1 is a potential therapeutic target for various cancer types, particularly those with high EGFR expression, but further research is needed to examine this hypothesis.
机译:亨廷顿病相互作用蛋白1(HIP1)与多种肿瘤类型相关。然而,其在肿瘤细胞中的确切功能尚不清楚。在这项研究中,研究了HIP1对EGFR降解的影响,该作用在EGF刺激后的致癌作用中具有重要作用。筛选17种细胞系后,在HeLa细胞中检测到HIP1和EGFR的共表达。因此,使用各种HIP1 siRNA序列在HeLa细胞中敲低了HIP1的表达。在各种浓度(即1.5和100 ng / ml)的EGF刺激后,检查EGFR的内吞作用和网格蛋白在HeLa细胞中的定位。在HIP1表达被siRNA阻断后,EGFR的内吞作用被加速,这种作用取决于EGF的浓度。这种内吞作用与网格蛋白表达共定位。这些发现表明对HIP1的抑制可以加速EGFR的内吞作用和降解。此外,他们认为HIP1是多种癌症的潜在治疗靶标,尤其是那些具有高EGFR表达的癌症,但是需要进一步的研究来检验这一假设。

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