CALD1 inhibits invasion of human ovarian cancer cells by affecting cytoskeletal structure and the number of focal adhesion.

IF 1.5 4区医学 Q4 ONCOLOGY

Translational cancer research Pub Date : 2025-02-28 Epub Date: 2025-02-24 DOI:10.21037/tcr-24-1375

Yongchao Li, Zhao Yang, Menglong Xu, Haocheng Guan, Zhenhui Wu, Shuwei Li

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引用次数: 0

Abstract

Background: Ovarian cancer (OV) is associated with the highest mortality rate among gynecological cancers, largely due to late diagnosis and chemoresistance. The identification of novel diagnostic markers and therapeutic targets is crucial. Caldesmon 1 (CALD1), a cytoskeleton-regulating protein, has been implicated in various cancers. This study aims to investigate the expression and functional significance of CALD1 in OV, focusing on its potential impact on cell invasion and metastasis.

Methods: We analyzed CALD1 expression using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, along with tissue microarray immunohistochemistry (IHC). Drug sensitivity analysis was performed using the 'oncopredict' R package. A CALD1 gene network was constructed, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. SK-OV-3 cell lines with stable CALD1 knockdown were established and verified by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot (WB). We then assessed cell invasiveness using Transwell assays and visualized cytoskeletal changes through immunofluorescence staining of F-actin and Vinculin.

Results: The expression of CALD1 was significantly reduced in OV tissues compared to normal tissues. Patients with high and low expression levels of CALD1 showed significant differences in their response to chemotherapeutic drugs. CALD1 and its related genes were found to play an essential role in regulating cytoskeleton organization, focal adhesion formation, and cell movement processes. CALD1 knockdown cells exhibited a significant reduction in F-actin stress fibers, a loose cytoskeleton structure, decreased Vinculin expression, and enhanced migration ability.

Conclusions: Attenuated expression of CALD1 in SK-OV-3 cells leads to fewer F-actin stress fibers, reducing the association between the cytoskeleton and Vinculin. This results in reduced cellular focal adhesions and increased invasiveness of SK-OV-3 cells, promoting OV cell metastasis. These findings suggest that CALD1 may have important clinical implications in the diagnosis and treatment of OV.

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CALD1通过影响细胞骨架结构和局灶黏附的数量来抑制人卵巢癌细胞的侵袭。

背景：卵巢癌（OV）是妇科癌症中死亡率最高的癌症，主要是由于晚期诊断和化疗耐药。确定新的诊断标记和治疗靶点是至关重要的。Caldesmon 1 （CALD1）是一种细胞骨架调节蛋白，与多种癌症有关。本研究旨在探讨CALD1在OV中的表达及其功能意义，重点探讨其对细胞侵袭转移的潜在影响。方法：我们使用癌症基因组图谱（TCGA）和基因型组织表达（GTEx）数据库以及组织微阵列免疫组化（IHC）分析CALD1的表达。使用“oncoppredict”R包进行药物敏感性分析。构建CALD1基因网络，进行基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析。建立CALD1稳定敲除的SK-OV-3细胞株，并采用实时荧光定量聚合酶链反应（qRT-PCR）和免疫印迹（WB）对其进行验证。然后，我们使用Transwell试验评估细胞侵袭性，并通过F-actin和Vinculin的免疫荧光染色观察细胞骨架的变化。结果：与正常组织相比，OV组织中CALD1的表达明显降低。CALD1高表达和低表达的患者对化疗药物的反应有显著差异。CALD1及其相关基因在调节细胞骨架组织、局灶黏附形成和细胞运动过程中发挥重要作用。CALD1敲低的细胞表现出F-actin应激纤维显著减少，细胞骨架结构松散，Vinculin表达降低，迁移能力增强。结论：SK-OV-3细胞中CALD1表达减弱导致F-actin应激纤维减少，降低了细胞骨架和Vinculin之间的关联。这导致细胞局灶黏附减少，SK-OV-3细胞的侵袭性增加，促进OV细胞转移。这些发现提示CALD1在OV的诊断和治疗中可能具有重要的临床意义。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Translational cancer research ONCOLOGY-

CiteScore

2.10

自引率

0.00%

发文量

252

期刊介绍： Translational Cancer Research (Transl Cancer Res TCR; Print ISSN: 2218-676X; Online ISSN 2219-6803; http://tcr.amegroups.com/) is an Open Access, peer-reviewed journal, indexed in Science Citation Index Expanded (SCIE). TCR publishes laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer; results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of cancer patients. The focus of TCR is original, peer-reviewed, science-based research that successfully advances clinical medicine toward the goal of improving patients'' quality of life. The editors and an international advisory group of scientists and clinician-scientists as well as other experts will hold TCR articles to the high-quality standards. We accept Original Articles as well as Review Articles, Editorials and Brief Articles.