Fascin-1 Identified as Driver of Cervical Cancer Spread and Drug Resistance

Fascin-1 Identified as Driver of Cervical Cancer Spread and Drug Resistance

June 13, 2025 Author Summary 0

A new study identifies a promising biomarker and target in cervical cancer

Cervical Cancer: Rising Threat Despite Standard Therapies

Cervical cancer (CC) continues to be one of the most common malignancies in women, currently ranking as the fourth most prevalent cancer worldwide. Epidemiological data show that high-risk human papillomavirus (HPV), particularly types HPV16 and HPV18, are responsible for the majority of cases. In recent years, the incidence of cervical cancer in women under 65 has increased, largely due to the growing prevalence of HPV infections and gaps in screening programs.

While surgery, radiation, and chemotherapy remain the mainstays of treatment, options for advanced or metastatic cases are limited. These challenges underscore the urgent need for new molecular targets that can improve the effectiveness of treatments and provide prognostic insight.

Investigating Fascin-1: A Cytoskeletal Protein with Oncogenic Potential

Fascin-1 is an actin-bundling protein known to be elevated in various metastatic cancers. Previous studies have suggested that it is involved in glycolysis regulation, epithelial–mesenchymal transition (EMT), chemoresistance, and cancer stemness. In cervical tissues, immunohistochemical analyses have shown low Fascin-1 levels in normal epithelium, with significantly higher levels observed in low- and high-grade intraepithelial neoplasia and cervical cancer tissues.

Despite these associations, the functional role and mechanisms of Fascin-1 in cervical cancer had not been fully clarified prior to this study.

Comprehensive Study Maps Fascin-1’s Role in Cervical Cancer

Researchers from The Fourth Hospital of Shijiazhuang designed a multifaceted investigation to examine how Fascin-1 contributes to cervical cancer cell growth, migration, metastasis, and drug response. Their methodology included:

  • Analysis of TCGA data and immunohistochemistry on patient tissues

  • Functional assays in cervical cancer cell lines (HeLa and C33A)

  • In vivo mouse xenograft and metastasis models

  • Molecular analysis of the Wnt/β-catenin signaling pathway

  • Drug sensitivity assays with cisplatin

Fascin-1 Is Overexpressed in Cervical Cancer Tissues

TCGA RNA-seq analysis revealed that Fascin-1 (FSCN1) mRNA is significantly upregulated in cervical cancer compared to normal cervical tissues. This finding was confirmed by immunohistochemical staining, which showed a higher level of Fascin-1 protein in cancerous tissues. Furthermore, a Kaplan–Meier survival analysis indicated that patients with higher Fascin-1 expression exhibited lower overall survival rates.

Fascin-1 Promotes Cervical Cancer Cell Growth

Lentiviral knockdown of FSCN1 in HeLa and C33A cells led to a marked reduction in cell proliferation, as shown by MTT and colony formation assays. Cell cycle analysis revealed G1-phase arrest in cells with reduced Fascin-1 expression. In contrast, overexpression of Fascin-1 enhanced proliferation and colony formation, suggesting a direct role in promoting tumor cell growth.

Fascin-1 Enhances Migration and Invasion

Transwell assays showed that Fascin-1 knockdown impaired both the migration and invasion of HeLa and C33A cells. When Fascin-1 was overexpressed, both traits were significantly enhanced. These effects were confirmed in mouse models, where Fascin-1 knockdown led to smaller tumors and reduced lung metastases in vivo.

Fascin-1 Regulates Wnt/β-Catenin Signaling Pathway

Gene Set Enrichment Analysis (GSEA) of RNA-seq data from Fascin-1-silenced HeLa cells indicated significant enrichment of the Wnt signaling pathway. Further assays showed that β-catenin and c-Myc expression were reduced at both RNA and protein levels following Fascin-1 knockdown, and increased upon overexpression.

Dual-luciferase reporter assays confirmed that Fascin-1 regulates Wnt/β-catenin transcriptional activity, identifying it as an upstream modulator of this signaling pathway.

Fascin-1 Knockdown Increases Cisplatin Sensitivity

Cisplatin is a widely used chemotherapy drug in cervical cancer treatment. The study found that Fascin-1 knockdown increased the sensitivity of cancer cells to cisplatin, as demonstrated by reduced proliferation and colony formation under treatment. This effect was also observed in vivo, where tumor volume and weight were significantly reduced in mice bearing Fascin-1-deficient tumors treated with cisplatin.

Migration and invasion assays further showed that Fascin-1 suppression, combined with cisplatin, reduced these aggressive behaviors more effectively than either treatment alone.

Practical Implications and Future Directions

This research establishes Fascin-1 as a key driver of cervical cancer growth, metastasis, and chemotherapy resistance. Its role in activating the Wnt/β-catenin pathway links it to a well-known oncogenic mechanism. These findings suggest several potential clinical applications:

  • Diagnostic marker: High Fascin-1 expression could help identify patients with more aggressive disease.

  • Therapeutic target: Silencing Fascin-1 may reduce tumor progression and enhance cisplatin efficacy.

Although specific Fascin-1 inhibitors are not yet standard in clinical use, the study mentions that a Fascin-1 inhibitor (NP-G2-044/DC05F01) is in phase II trials for solid tumors.

 

The translation of the preceding English text in Chinese:

 

一项新研究确定了宫颈癌中的有前景的生物标志物和治疗靶点


宫颈癌：尽管有标准治疗，威胁仍在上升

宫颈癌（Cervical Cancer，CC）仍然是女性最常见的恶性肿瘤之一，目前在全球女性癌症中排名第四。流行病学数据显示，高危型人乳头瘤病毒（HPV），尤其是HPV16和HPV18，是大多数宫颈癌病例的致病因素。近年来，65岁以下女性的宫颈癌发病率有所上升，主要原因是HPV感染的增加以及筛查项目存在的空白。

尽管手术、放疗和化疗仍是主要治疗手段，但对于晚期或转移性病例，治疗选择依然有限。这些挑战凸显了亟需新的分子靶点，以提高治疗效果并提供预后信息。

研究Fascin-1：一种具有致癌潜力的细胞骨架蛋白

Fascin-1是一种肌动蛋白束缚蛋白，在多种转移性癌症中表达升高。既往研究表明，Fascin-1参与糖酵解调控、上皮-间充质转化（EMT）、化疗耐药以及癌症干性。在宫颈组织中，免疫组化分析显示，正常上皮中Fascin-1表达较低，而在低级别和高级别上皮内瘤变及宫颈癌组织中表达显著升高。

尽管已观察到这些关联，但Fascin-1在宫颈癌中的功能作用和机制在本研究之前尚未完全阐明。

全面研究描绘Fascin-1在宫颈癌中的作用

石家庄市第四医院的研究人员设计了多层次的研究来探讨Fascin-1在宫颈癌细胞生长、迁移、转移及药物反应中的作用。他们的研究方法包括：

  • TCGA数据库分析及患者组织的免疫组化染色

  • 宫颈癌细胞系（HeLa和C33A）的功能实验

  • 小鼠体内移植瘤和转移模型

  • Wnt/β-catenin信号通路的分子分析

  • 顺铂药物敏感性实验

Fascin-1在宫颈癌组织中过表达

TCGA RNA测序分析发现，与正常宫颈组织相比，宫颈癌组织中Fascin-1（FSCN1）mRNA水平显著上调。免疫组化染色进一步证实，癌组织中的Fascin-1蛋白表达更高。Kaplan–Meier生存分析显示，Fascin-1表达较高的患者总体生存率较低。

Fascin-1促进宫颈癌细胞生长

在HeLa和C33A细胞中通过慢病毒敲低FSCN1显著抑制了细胞增殖，MTT和克隆形成实验均证实了这一点。细胞周期分析显示，Fascin-1敲低细胞停滞于G1期。相反，Fascin-1过表达增强了增殖和克隆形成能力，提示其直接促进肿瘤细胞生长。

Fascin-1增强细胞迁移和侵袭能力

Transwell实验表明，敲低Fascin-1可显著抑制HeLa和C33A细胞的迁移和侵袭能力。而Fascin-1过表达则增强了这些行为。在小鼠模型中，敲低Fascin-1导致肿瘤体积更小、肺转移减少，进一步验证了其促转移作用。

Fascin-1调控Wnt/β-Catenin信号通路

在Fascin-1沉默的HeLa细胞中进行的RNA测序富集分析（GSEA）发现Wnt信号通路显著富集。进一步实验显示，敲低Fascin-1会降低β-catenin和c-Myc的RNA和蛋白表达水平，而过表达则相反。

双荧光素酶报告基因实验证实，Fascin-1调控Wnt/β-catenin的转录活性，是该信号通路的上游调节因子。

Fascin-1敲低增加顺铂敏感性

顺铂是治疗宫颈癌常用的化疗药物。本研究发现，敲低Fascin-1可增强癌细胞对顺铂的敏感性，表现为在顺铂处理下细胞增殖和克隆形成减少。在体内实验中，Fascin-1敲低小鼠模型在接受顺铂治疗后，肿瘤体积和重量明显减小。

迁移和侵袭实验进一步显示，Fascin-1沉默与顺铂联合使用比单独治疗更有效地抑制这些侵袭行为。

现实意义与未来方向

本研究确立了Fascin-1在宫颈癌生长、转移和耐药中的关键作用。其通过激活Wnt/β-catenin信号通路与已知致癌机制相联系。这些发现表明其在临床上具有多种潜在用途：

  • 诊断标志物：Fascin-1高表达可用于识别更具侵袭性的患者。

  • 治疗靶点：抑制Fascin-1可减缓肿瘤进展并增强顺铂疗效。

虽然Fascin-1特异性抑制剂目前尚未临床常规使用，但研究中提到的一种Fascin-1抑制剂（NP-G2-044/DC05F01）已进入针对实体瘤的II期临床试验。

Reference:

Yan Wang, Wei Cui, Dong-Mei Chu

Role of Fascin-1 in cervical cancer metastasis via Wnt/β-catenin pathway activation.

Biomol Biomed [Internet]. 2025 Mar. 14 [cited 2025 Jun. 11];

Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/12114

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Editor: Merima Hadžić

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