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Precancerous microenvironment: A signalling perspective 癌前微环境：信号视角
IF 4.3 2区 生物学 Q1 CELL BIOLOGY
Current Opinion in Cell Biology
Pub Date : 2026-01-07 DOI: 10.1016/j.ceb.2025.102611
Xiao Qin
The progression from healthy tissue to malignancy involves a critical precancerous stage marked by cellular lesions with aberrant molecular and phenotypic characteristics. The fate of these lesions is shaped not only by cell-intrinsic alterations but also by the precancerous microenvironment (PME), an ecosystem of epithelial, stromal and immune cells embedded within the extracellular matrix. Focusing on epithelial precancers, this review first defines the metastable state and signalling networks that distinguish precancer from homeostasis and cancer. It then examines the models and technologies used to investigate PME signalling across spatial–temporal dimensions, followed by an integrated overview of how PME components collectively shape lesion trajectories. Finally, it outlines the outstanding questions and research priorities needed to advance mechanistic insight and realise the translational potential of PME-targeted interventions.
从健康组织到恶性肿瘤的进展涉及一个关键的癌前阶段，其特征是细胞病变具有异常的分子和表型特征。这些病变的命运不仅受到细胞内在改变的影响，还受到癌前微环境（PME）的影响，PME是一种由细胞外基质内嵌的上皮细胞、基质细胞和免疫细胞组成的生态系统。本综述以上皮癌前病变为重点，首先定义了区分癌前病变与体内平衡和癌症的亚稳态和信号网络。然后，研究了用于跨时空维度研究PME信号的模型和技术，随后综合概述了PME组件如何共同塑造病变轨迹。最后，它概述了突出的问题和研究重点，需要推进机制的洞察力和实现pme目标干预的转化潜力。
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引用次数: 0
Renaissance at the actin filament pointed end: Mechanisms of assembly, capping and depolymerization 肌动蛋白丝尖端的再生：组装、旋盖和解聚的机制。
IF 4.3 2区 生物学 Q1 CELL BIOLOGY
Current Opinion in Cell Biology
Pub Date : 2025-12-24 DOI: 10.1016/j.ceb.2025.102602
Shashank Shekhar , Velia M. Fowler , Carol C. Gregorio
Cellular and biochemical studies of actin assembly have long focused primarily on reactions at the fast-growing barbed end of actin filaments. In contrast, the slow-growing pointed end has traditionally received comparatively less attention. Recent structural, biochemical, and cell biological studies have sparked a renaissance in pointed-end research, revealing its active roles in both actin assembly and disassembly. The discovery of pointed-end polymerization by the bacterial effector VopF has challenged the barbed-end centric assembly paradigm and reinvigorated efforts to identify endogenous pointed-end elongators. This review highlights the emerging molecular machinery and mechanisms governing pointed-end dynamics, including nucleation, elongation, capping, and disassembly. We discuss the physiological significance of pointed-end regulation and argue that a comprehensive understanding of actin regulation requires close attention to pointed end dynamics.
长期以来，对肌动蛋白组装的细胞和生化研究主要集中在肌动蛋白丝快速生长的倒钩端的反应上。相比之下，生长缓慢的尖端传统上受到的关注相对较少。最近的结构、生化和细胞生物学研究引发了尖端研究的复兴，揭示了它在肌动蛋白组装和拆卸中的积极作用。细菌效应物VopF的尖端聚合的发现挑战了倒钩端中心组装范式，并重新激活了鉴定内源性尖端延长子的努力。这篇综述强调了新兴的分子机制和控制尖端动力学的机制，包括成核、延伸、封盖和拆卸。我们讨论了尖端调控的生理意义，并认为对肌动蛋白调控的全面理解需要密切关注尖端动力学。
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引用次数: 0
Network structures and parameters in multiscale modeling in ErbB signaling networks ErbB信令网络多尺度建模中的网络结构和参数
IF 4.3 2区 生物学 Q1 CELL BIOLOGY
Current Opinion in Cell Biology
Pub Date : 2025-12-10 DOI: 10.1016/j.ceb.2025.102603
Ai Shinobu , Ayaka Nagasato-Ichikawa , Mariko Okada
Signal transduction is a complex system governing cellular behavior across physiological and pathological contexts. Advances in systems biology have positioned cell modeling as a powerful tool for reconstructing the dynamics and trajectories of disease processes. Nevertheless, despite progress in AI-assisted model generation, parameter estimation remains a challenge, especially under data constraints. In contrast, molecular dynamics simulations offer crucial, high-resolution insights by uncovering conformational activation mechanisms and by extracting kinetic parameters; however, they face scalability limitations. This review focuses on modeling of the ErbB signaling system, highlighting recent advances at both the cellular and molecular scales. Emerging trends, such as simulation data reuse, machine learning-guided network inference, and modeling within realistic environmental contexts, are now driving a compelling integration of these molecular and cellular modeling paradigms.
信号转导是一个复杂的系统，在生理和病理背景下控制细胞行为。系统生物学的进步已经将细胞建模定位为重建疾病过程的动力学和轨迹的有力工具。然而，尽管人工智能辅助模型生成取得了进展，但参数估计仍然是一个挑战，特别是在数据约束下。相比之下，分子动力学模拟通过揭示构象激活机制和提取动力学参数，提供了至关重要的高分辨率见解；然而，它们面临着可伸缩性的限制。本文综述了ErbB信号系统的建模，重点介绍了细胞和分子尺度上的最新进展。新兴趋势，如模拟数据重用、机器学习引导的网络推理和现实环境中的建模，正在推动这些分子和细胞建模范式的引人注目的整合。
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引用次数: 0
Cancer-associated fibroblasts: Recent advances and therapeutic implications 癌症相关成纤维细胞：最新进展及其治疗意义
IF 4.3 2区 生物学 Q1 CELL BIOLOGY
Current Opinion in Cell Biology
Pub Date : 2025-12-01 DOI: 10.1016/j.ceb.2025.102601
Christina Paraskeva , Athanasia Stavropoulou , Vasiliki Koliaraki
The tumor microenvironment (TME) plays a crucial role in cancer initiation, progression, and metastasis, with cancer-associated fibroblasts (CAFs) representing one of the most abundant and influential stromal cell populations. Recent advances in single cell sequencing and spatial transcriptomics in combination with mechanistic studies have revealed the extent of CAF functional heterogeneity, identifying distinct subpopulations with specialized roles in tumor promotion, immune modulation, and therapy resistance. This review synthesizes current understanding of CAF biology, highlighting recent discoveries regarding their spatial organization, temporal dynamics, and immunoregulatory functions. We discuss emerging therapeutic strategies targeting CAF subpopulations, including approaches for CAF elimination and reprogramming. These advances provide new opportunities for developing more effective cancer treatments that account for stromal complexity and CAF-mediated resistance mechanisms.
肿瘤微环境（TME）在癌症的发生、进展和转移中起着至关重要的作用，而癌症相关成纤维细胞（CAFs）是最丰富和最具影响力的基质细胞群之一。单细胞测序和空间转录组学的最新进展与机制研究相结合，揭示了CAF功能异质性的程度，确定了在肿瘤促进、免疫调节和治疗抵抗中具有特殊作用的不同亚群。本文综述了目前对CAF生物学的理解，重点介绍了它们在空间组织、时间动态和免疫调节功能方面的最新发现。我们讨论了针对CAF亚群的新兴治疗策略，包括CAF消除和重编程的方法。这些进展为开发更有效的癌症治疗提供了新的机会，这些治疗可以解释基质复杂性和cafc介导的耐药机制。
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引用次数: 0
Outside Back Cover 外封底
IF 4.3 2区 生物学 Q1 CELL BIOLOGY
Current Opinion in Cell Biology
Pub Date : 2025-12-01 DOI: 10.1016/S0955-0674(25)00148-6
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引用次数: 0
Ras signalling at the actin cortex: Coordinating local and global changes to cell morphology 肌动蛋白皮层的Ras信号：协调局部和整体细胞形态的变化
IF 4.3 2区 生物学 Q1 CELL BIOLOGY
Current Opinion in Cell Biology
Pub Date : 2025-11-22 DOI: 10.1016/j.ceb.2025.102600
Joe J. Tyler, Helen K. Matthews
Ras proteins modulate key cellular signalling pathways and drive excessive proliferation when mutated in cancer. However, they also influence actin cytoskeleton organisation. In the model organism Dictyostelium, domains of active Ras pattern the plasma membrane and locally reorganise the actin cortex, driving the formation of actin-based protrusions. Recent work has identified analogous Ras-dependent actin structures in cancer cells, including actin waves, protrusions and membrane blebs, which promote cell survival and motility. In addition, Ras activation induces changes to signalling networks and gene expression that result in cell-wide changes to actin network architecture, cortex mechanics and cell shape. This review examines how the local and global effects of Ras signalling on the actin cytoskeleton are coordinated and how they contribute to cytoskeletal plasticity during cancer progression.
Ras蛋白调节关键的细胞信号通路，并在癌症中发生突变时驱动过度增殖。然而，它们也影响肌动蛋白细胞骨架组织。在模式生物盘基骨柱中，活性Ras结构域影响质膜，局部重组肌动蛋白皮层，驱动肌动蛋白基突起的形成。最近的研究已经在癌细胞中发现了类似的ras依赖的肌动蛋白结构，包括肌动蛋白波、突起和膜泡，它们促进细胞存活和运动。此外，Ras激活诱导信号网络和基因表达的变化，导致细胞范围内肌动蛋白网络结构、皮质力学和细胞形状的变化。本文综述了Ras信号对肌动蛋白细胞骨架的局部和全局影响是如何协调的，以及它们在癌症进展过程中如何促进细胞骨架的可塑性。
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引用次数: 0
Driving cancer: Motor and adaptor protein dysregulation in endocytic receptor signalling 驱动癌症：内吞受体信号传导中的运动和衔接蛋白失调。
IF 4.3 2区 生物学 Q1 CELL BIOLOGY
Current Opinion in Cell Biology
Pub Date : 2025-11-17 DOI: 10.1016/j.ceb.2025.102598
David H. Kim , Shreya E. Boby , Gregory M.I. Redpath, Vaishnavi Ananthanarayanan
Receptor tyrosine kinases and other cell surface receptors are tightly regulated by endocytosis, which controls both the duration and spatial organisation of their downstream signalling. In cancers, altered internalisation and trafficking lead to sustained or misrouted signalling that promotes uncontrolled cell growth and survival. Motor proteins and their cargo adaptors are central to receptor signalling since they determine intracellular endosome positioning, recycling, and degradation. While their roles in intracellular transport have long been studied, the dysfunction of motors and adaptors in the context of aberrant receptor signalling and cancer progression has only recently begun to emerge. In this review, we highlight recent advances in understanding motor and adaptor function in healthy cells, discuss evidence implicating these proteins in oncogenic signalling, and consider how these insights may guide future directions in the field.
受体酪氨酸激酶和其他细胞表面受体受到内吞作用的严格调节，内吞作用控制着其下游信号传导的持续时间和空间组织。在癌症中，内化和运输的改变会导致持续或错误的信号传导，从而促进不受控制的细胞生长和存活。运动蛋白及其载货接头是受体信号传导的核心，因为它们决定细胞内核内体的定位、再循环和降解。虽然它们在细胞内运输中的作用已经被研究了很长时间，但在异常受体信号传导和癌症进展的背景下，马达和接头的功能障碍最近才开始出现。在这篇综述中，我们重点介绍了在理解健康细胞中的运动和接头功能方面的最新进展，讨论了这些蛋白质在致癌信号传导中的证据，并考虑了这些见解如何指导该领域的未来方向。
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引用次数: 0
Corrigendum to Exploring the dynamic behavior of leukocytes with zebrafish Curr Opin Cell Biol 85 December 2023 102276- 探索斑马鱼白细胞动态行为的勘误表细胞生物学85十二月2023 102276-
IF 4.3 2区 生物学 Q1 CELL BIOLOGY
Current Opinion in Cell Biology
Pub Date : 2025-11-14 DOI: 10.1016/j.ceb.2025.102599
Cassia Michael , Sofia de Oliveira
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引用次数: 0
Single-molecule biophysics in signaling: Functionality from stochastic effects 信号传导中的单分子生物物理学：随机效应的功能
IF 4.3 2区 生物学 Q1 CELL BIOLOGY
Current Opinion in Cell Biology
Pub Date : 2025-11-08 DOI: 10.1016/j.ceb.2025.102597
Jay T. Groves
The growing ease with which single molecules can be visualized in living systems is providing a fantastic new view into the molecular processes of cellular signal transduction. The single-molecule perspective reveals stochastic variation and molecular heterogeneity in unaveraged detail and is revealing new mechanisms by which biological functionality is physically achieved. Here we discuss several examples of newly emerging signaling mechanisms intrinsically rooted in the stochastic realm. The common theme is a competitive enzymatic reaction cycle with the substrate and product localized to the membrane, while the controlling enzymes reside in the cytosol. This general reaction configuration is extremely common among signaling systems, and some quite unexpected behaviors can be observed when the functional system includes only a small number of molecules.
单个分子在生命系统中的可视化日益容易，这为细胞信号转导的分子过程提供了一个奇妙的新视角。单分子视角揭示了非平均细节的随机变化和分子异质性，并揭示了生物功能物理实现的新机制。在这里，我们讨论了几个新出现的信号机制的例子，这些机制本质上植根于随机领域。共同的主题是一个竞争性的酶促反应循环，底物和产物定位于膜，而控制酶驻留在细胞质中。这种一般的反应构型在信号系统中非常常见，当功能系统只包含少量分子时，可以观察到一些非常意想不到的行为。
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引用次数: 0
When two worlds collide: actin dynamics on endomembranes regulates membrane trafficking 当两个世界碰撞：肌动蛋白在膜上的动力学调节膜运输
IF 4.3 2区 生物学 Q1 CELL BIOLOGY
Current Opinion in Cell Biology
Pub Date : 2025-11-01 DOI: 10.1016/j.ceb.2025.102596
Michelle F. Marchan , James E. Bear
Membrane trafficking is an essential aspect of cellular physiology, determining the spatial distribution of macromolecules within a cell in response to conditions such as nutrient availability and cellular stress. Much of this trafficking happens at intracellular membrane delimited vesicles and organelles—here referred to as endomembranes. Actin cytoskeletal dynamics contribute to intracellular force production, including fueling aspects of membrane trafficking on endomembranes. Cellular membrane trafficking and actin dynamics have traditionally been studied as separate specializations. Yet, actin networks interact with membranes and contribute to membrane remodeling, organelle motility, and cargo sorting. Here, we propose a conceptual framework for how actin filament networks participate in endomembrane trafficking and describe examples of each of the putative functions. Furthermore, we describe how aberrant actin-endomembrane interactions contribute to disease states and pose some open questions for the field.
膜运输是细胞生理学的一个重要方面，决定了细胞内大分子的空间分布，以响应诸如营养可用性和细胞应激等条件。这种运输大部分发生在细胞膜内的小泡和细胞器，这里称为内膜。肌动蛋白细胞骨架动力学有助于细胞内力的产生，包括促进膜内运输。细胞膜运输和肌动蛋白动力学传统上被视为单独的专业研究。然而，肌动蛋白网络与膜相互作用，并有助于膜重塑，细胞器运动和货物分类。在这里，我们提出了肌动蛋白丝网络如何参与膜运输的概念框架，并描述了每个假定功能的例子。此外，我们描述了异常的肌动蛋白-膜相互作用如何导致疾病状态，并为该领域提出了一些悬而未决的问题。
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