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高基质硬度通过整合素β1-网蛋白-F-肌动蛋白轴加速肝癌细胞迁移。

High matrix stiffness accelerates migration of hepatocellular carcinoma cells through the integrin β1-Plectin-F-actin axis.

作者信息

Wang Zhihui, Wang Wenbin, Luo Qing, Song Guanbin

机构信息

College of Bioengineering, Chongqing University, Chongqing, 400030, China.

Key Laboratory of Biorheological Science & Technology, Ministry of Education, Chongqing University, Chongqing, 400030, China.

出版信息

BMC Biol. 2025 Jan 9;23(1):8. doi: 10.1186/s12915-025-02113-1.

DOI:10.1186/s12915-025-02113-1
PMID:39789506
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11721467/
Abstract

BACKGROUND

Abundant research indicates that increased extracellular matrix (ECM) stiffness significantly enhances the malignant characteristics of hepatocellular carcinoma (HCC) cells. Plectin, an essential cytoskeletal linker protein, has recently emerged as a promoter of cancer progression, particularly in the context of cancer cell invasion and metastasis. However, the responsiveness of plectin to changes in ECM stiffness and its impact on HCC progression remain unclear. In this study, we aimed to investigate whether plectin responds to variations in ECM stiffness and to explore its involved molecular mechanisms in regulating HCC cell migration.

RESULTS

Our results showed that, when compared with control group (7 kPa), high ECM stiffness (53 kPa) boosts HCC cell migration by upregulating plectin and integrin β1 expression and increasing F-actin polymerization. Knockdown of integrin β1 negated the high stiffness-upregulated plectin expression. Furthermore, reducing either plectin or integrin β1 levels, or using latrunculin A, effectively prevented the high ECM stiffness-induced F-actin polymerization and HCC cell migration.

CONCLUSIONS

These findings demonstrate that integrin β1-plectin-F-actin axis is necessary for high matrix stiffness-driven migration of HCC cells, and provide evidence for the critical role of plectin in mechanotransduction in HCC cells.

摘要

背景

大量研究表明,细胞外基质(ECM)硬度增加会显著增强肝细胞癌(HCC)细胞的恶性特征。网蛋白是一种重要的细胞骨架连接蛋白,最近已成为癌症进展的促进因子,尤其是在癌细胞侵袭和转移方面。然而,网蛋白对ECM硬度变化的反应及其对HCC进展的影响仍不清楚。在本研究中,我们旨在研究网蛋白是否对ECM硬度变化有反应,并探索其在调节HCC细胞迁移中涉及的分子机制。

结果

我们的结果表明,与对照组(7千帕)相比,高ECM硬度(53千帕)通过上调网蛋白和整合素β1表达以及增加F-肌动蛋白聚合来促进HCC细胞迁移。整合素β1的敲低消除了高硬度上调的网蛋白表达。此外,降低网蛋白或整合素β1水平,或使用拉春库林A,可有效阻止高ECM硬度诱导的F-肌动蛋白聚合和HCC细胞迁移。

结论

这些发现表明,整合素β1-网蛋白-F-肌动蛋白轴对于高基质硬度驱动的HCC细胞迁移是必需的,并为网蛋白在HCC细胞机械转导中的关键作用提供了证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9796/11721467/e82bdc59d38e/12915_2025_2113_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9796/11721467/a13c9210c253/12915_2025_2113_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9796/11721467/53f1467cc49f/12915_2025_2113_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9796/11721467/982be68aa6d4/12915_2025_2113_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9796/11721467/b760c1ac2aa3/12915_2025_2113_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9796/11721467/520c963615b8/12915_2025_2113_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9796/11721467/502992aa2b70/12915_2025_2113_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9796/11721467/e82bdc59d38e/12915_2025_2113_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9796/11721467/a13c9210c253/12915_2025_2113_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9796/11721467/53f1467cc49f/12915_2025_2113_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9796/11721467/982be68aa6d4/12915_2025_2113_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9796/11721467/b760c1ac2aa3/12915_2025_2113_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9796/11721467/520c963615b8/12915_2025_2113_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9796/11721467/502992aa2b70/12915_2025_2113_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9796/11721467/e82bdc59d38e/12915_2025_2113_Fig7_HTML.jpg

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The extracellular matrix as hallmark of cancer and metastasis: From biomechanics to therapeutic targets.细胞外基质作为癌症和转移的标志:从生物力学到治疗靶点。
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