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波形肌动蛋白3作为一种肌动蛋白结合蛋白在三阴性乳腺癌病理中的作用

Role of WAVE3 as an actin binding protein in the pathology of triple negative breast cancer.

作者信息

Master Kruyanshi, El Khalki Lamyae, Bayachou Mekki, Sossey-Alaoui Khalid

机构信息

Department of Chemistry, Cleveland State University, Cleveland, Ohio, USA.

MetroHealth System, Cleveland, Ohio, USA.

出版信息

Cytoskeleton (Hoboken). 2025 Mar;82(3):130-144. doi: 10.1002/cm.21898. Epub 2024 Jul 18.

Abstract

Breast cancer, a prevalent global health concern, has sparked extensive research efforts, particularly focusing on triple negative breast cancer (TNBC), a subtype lacking estrogen receptor (ER), progesterone receptor, and epidermal growth factor receptor. TNBC's aggressive nature and resistance to hormone-based therapies heightens the risk of tumor progression and recurrence. Actin-binding proteins, specifically WAVE3 from the Wiskott-Aldrich syndrome protein (WASP) family, have emerged as major drivers in understanding TNBC biology. This review delves into the intricate molecular makeup of TNBC, shedding light on actin's fundamental role in cellular processes. Actin, a structural element in the cytoskeleton, regulates various cellular pathways essential for homeostasis. Its dynamic nature enables functions such as cell migration, motility, intracellular transport, cell division, and signal transduction. Actin-binding proteins, including WAVE3, play pivotal roles in these processes. WAVE3, a member of the WASP family, remains the focus of this review due to its potential involvement in TNBC progression. While actin-binding proteins are studied for their roles in healthy cellular cycles, their significance in TNBC remains underexplored. This review aims to discuss WAVE3's impact on TNBC, exploring its molecular makeup, functions, and significance in tumor progression. The intricate structure of WAVE3, featuring elements like the verprolin-cofilin-acidic domain and regulatory elements, plays a crucial role in regulating actin dynamics. Dysregulation of WAVE3 in TNBC has been linked to enhanced cell migration, invasion, extracellular matrix remodeling, epithelial-mesenchymal transition, tumor proliferation, and therapeutic resistance. Understanding the role of actin-binding proteins in cancer biology has potential clinical implications, making them potential prognostic biomarkers and promising therapeutic targets. The review emphasizes the need for further research into actin-binding proteins' clinical applications, diagnostic value, and therapeutic interventions. In conclusion, this comprehensive review explores the complex interplay between actin and actin-binding proteins, with special emphasis on WAVE3, in the context of TNBC. By unraveling the molecular intricacies, structural characteristics, and functional significance, the review paves the way for future research directions, clinical applications, and potential therapeutic strategies in the challenging landscape of TNBC.

摘要

乳腺癌是一个全球普遍关注的健康问题,引发了广泛的研究努力,尤其聚焦于三阴性乳腺癌(TNBC),这是一种缺乏雌激素受体(ER)、孕激素受体和表皮生长因子受体的亚型。TNBC的侵袭性本质以及对基于激素的疗法的耐药性增加了肿瘤进展和复发的风险。肌动蛋白结合蛋白,特别是威斯科特-奥尔德里奇综合征蛋白(WASP)家族中的WAVE3,已成为理解TNBC生物学特性的主要驱动因素。本综述深入探讨TNBC复杂的分子构成,揭示肌动蛋白在细胞过程中的基础作用。肌动蛋白是细胞骨架的一种结构成分,调节维持体内平衡所必需的各种细胞途径。其动态特性使其能够发挥诸如细胞迁移、运动、细胞内运输、细胞分裂和信号转导等功能。包括WAVE3在内的肌动蛋白结合蛋白在这些过程中发挥着关键作用。WAVE3作为WASP家族的一员,因其可能参与TNBC进展而仍是本综述的重点。虽然肌动蛋白结合蛋白在健康细胞周期中的作用已得到研究,但其在TNBC中的重要性仍未得到充分探索。本综述旨在讨论WAVE3对TNBC的影响,探索其分子构成、功能以及在肿瘤进展中的意义。WAVE3的复杂结构,包括诸如维普洛林-丝切蛋白-酸性结构域和调节元件等成分,在调节肌动蛋白动力学方面起着关键作用。TNBC中WAVE3的失调与细胞迁移增强、侵袭、细胞外基质重塑、上皮-间质转化、肿瘤增殖和治疗耐药性有关。了解肌动蛋白结合蛋白在癌症生物学中的作用具有潜在的临床意义,使其成为潜在的预后生物标志物和有前景的治疗靶点。本综述强调需要进一步研究肌动蛋白结合蛋白的临床应用、诊断价值和治疗干预措施。总之,本全面综述探讨了在TNBC背景下肌动蛋白与肌动蛋白结合蛋白之间的复杂相互作用,特别强调了WAVE3。通过揭示分子复杂性、结构特征和功能意义,本综述为TNBC这一具有挑战性领域的未来研究方向、临床应用和潜在治疗策略铺平了道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b656/11904861/687528717f45/CM-82-130-g003.jpg

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