B7-H3 通过调节肌动蛋白细胞骨架和 RhoA/ROCK1/LIMK1 信号通路促进结直肠癌细胞的迁移和侵袭

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS
Anjing Zhao , Xingchao Zhu , Hongya Wu , Jiayu Wang , Mengting Zhang , Jingrong Xiang , Suhua Xia , Tongguo Shi , Qinhua Xi
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引用次数: 0

摘要

背景和目的已在包括结直肠癌(CRC)在内的多种癌症中检测到 B7 同源物 3 蛋白(B7-H3)的大量表达,并被认为与调节 CRC 细胞的多种生物功能有关。然而,它在 CRC 转移中的作用尚未确定。本研究旨在探索和揭示 B7-H3 促进 CRC 迁移、侵袭和肌动蛋白细胞骨架的潜在机制。进行Transwell和F-肌动蛋白免疫荧光染色,以探讨B7-H3在CRC细胞迁移、侵袭和肌动蛋白丝堆积中的作用。结果 B7-H3 在 CRC 组织中高表达,并且通过免疫组化与 CRC 患者的不良预后呈正相关。迁移和侵袭实验表明,敲除 B7-H3 能显著抑制 CRC 细胞的迁移和侵袭。B7-H3 过表达则有相反的效果。此外,我们还通过F-肌动蛋白免疫荧光染色和Western印迹确定了B7-H3可以调控肌动蛋白细胞骨架和RhoA/ROCK1/LIMK1通路。重要的是,RhoA/ROCK1/(LIM domain kinase 1)LIMK1 轴抑制剂 BDP5290 逆转了 B7-H3 过表达对 CRC 细胞肌动蛋白丝堆积、迁移和侵袭的影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
B7-H3 promotes the migration and invasion of colorectal cancer cells via regulating the actin cytoskeleton and RhoA/ROCK1/LIMK1 signaling pathway

Background and aims

Aberrant expression of B7 homolog 3 protein (B7-H3) has been detected in various cancers including colorectal cancer (CRC) and implicated in modulating multiple biological functions of CRC cells. However, its role in CRC metastasis has not yet been determined. This study aims to explore and unravel the underlying mechanisms through which B7-H3 contributes to migration, invasion and actin cytoskeleton in CRC.

Methods

The expression of B7-H3 and LIMK1 in CRC tumor samples was determined by IHC staining. Transwell and F-actin immunofluorescence staining assays were performed to explore the role of B7-H3 in migration, invasion and actin filament accumulating of CRC cells. RNA-seq and Western blot assays were used to investigate the molecular mechanisms.

Results

B7-H3 was highly expressed in CRC tissues and positively associated with poor prognosis of CRC patients by immunohistochemistry. Migration and invasion assays showed that B7-H3 knockdown significantly inhibited the migration and invasion of CRC cells. B7-H3 overexpression had the opposite effect. Moreover, we determined that B7-H3 could regulate actin cytoskeleton and the RhoA/ROCK1/LIMK1 pathway by F-actin immunofluorescence staining and Western blot. Importantly, the BDP5290, an inhibitor of the RhoA/ROCK1/(LIM domain kinase 1) LIMK1 axis, reversed the effects of B7-H3 overexpression on actin filament accumulating, migration, and invasion of CRC cells.

Conclusions

Our study concluded that B7-H3 facilitated CRC cell actin filament accumulating, migration, and invasion through the RhoA/ROCK1/LIMK1 axis.

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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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