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Advisory Board and Contents 咨询委员会和内容
IF 19 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-05-02 DOI: 10.1016/s0962-8924(24)00077-1
No Abstract
无摘要
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引用次数: 0
Multifaceted collagen-DDR1 signaling in cancer. 癌症中的多方面胶原-DDR1信号传导。
IF 13 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-05-01 Epub Date: 2023-09-12 DOI: 10.1016/j.tcb.2023.08.003
Hua Su, Michael Karin

In addition to immune cells and fibroblasts, the tumor microenvironment (TME) comprises an extracellular matrix (ECM) which contains collagens (COLs) whose architecture and remodeling dictate cancer development and progression. COL receptors expressed by cancer cells sense signals generated by microenvironmental alterations in COL state to regulate cell behavior and metabolism. Discoidin domain receptor 1 (DDR1) is a key sensor of COL fiber state and composition that controls tumor cell metabolism and growth, response to therapy, and patient survival. This review focuses on DDR1 to NRF2 signaling, its modulation of autophagy and macropinocytosis (MP), and its role in cancer and other diseases. Elucidating the regulation of DDR1 activity and expression under different pathophysiological conditions will facilitate the discovery of new therapeutics.

除了免疫细胞和成纤维细胞外,肿瘤微环境(TME)还包括细胞外基质(ECM),其含有胶原蛋白(COL),胶原蛋白的结构和重塑决定了癌症的发展和进展。癌症细胞表达的COL受体感知由COL状态的微环境改变产生的信号,以调节细胞行为和代谢。盘状蛋白结构域受体1(DDR1)是COL纤维状态和组成的关键传感器,控制肿瘤细胞代谢和生长、对治疗的反应和患者生存。这篇综述的重点是DDR1-NRF2信号,它对自噬和大细胞增多症(MP)的调节,以及它在癌症和其他疾病中的作用。阐明DDR1活性和表达在不同病理生理条件下的调节将有助于发现新的治疗方法。
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引用次数: 0
Towards solving the mystery of peroxisomal matrix protein import. 致力于解开过氧化物酶体基质蛋白进口之谜。
IF 13 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-05-01 Epub Date: 2023-09-22 DOI: 10.1016/j.tcb.2023.08.005
Michael L Skowyra, Peiqiang Feng, Tom A Rapoport

Peroxisomes are vital metabolic organelles that import their lumenal (matrix) enzymes from the cytosol using mobile receptors. Surprisingly, the receptors can even import folded proteins, but the underlying mechanism has been a mystery. Recent results reveal how import receptors shuttle cargo into peroxisomes. The cargo-bound receptors move from the cytosol across the peroxisomal membrane completely into the matrix by a mechanism that resembles transport through the nuclear pore. The receptors then return to the cytosol through a separate retrotranslocation channel, leaving the cargo inside the organelle. This cycle concentrates imported proteins within peroxisomes, and the energy for cargo import is supplied by receptor export. Peroxisomal protein import thus fundamentally differs from other previously known mechanisms for translocating proteins across membranes.

过氧化物酶体是重要的代谢细胞器,通过移动受体从胞质溶胶中导入其内腔(基质)酶。令人惊讶的是,受体甚至可以导入折叠的蛋白质,但其潜在机制一直是个谜。最近的研究结果揭示了进口受体如何将货物穿梭到过氧化物酶体中。货物结合受体通过类似于通过核孔运输的机制从胞质溶胶穿过过氧化物酶体膜完全进入基质。受体然后通过一个单独的反转录通道返回胞质溶胶,将货物留在细胞器内。这个循环将进口蛋白质集中在过氧化物酶体中,货物进口的能量由受体出口提供。因此,过氧化物酶体蛋白质的输入与其他先前已知的蛋白质跨膜转运机制有根本不同。
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引用次数: 0
A20: a jack of all trades. A20:万事通。
IF 13 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-05-01 Epub Date: 2024-03-09 DOI: 10.1016/j.tcb.2024.02.008
Pieter Hertens, Geert van Loo

Mutations and polymorphisms in A20/TNFAIP3 have been linked to various inflammatory disorders. However, in addition to its well-known role in inflammation, A20 also controls EDAR- and receptor activator of NF-κB (RANK)-induced NF-κB signaling, regulating the development of epidermal skin appendages and bone, respectively. Furthermore, A20 regulates synapse remodeling through a mechanism dependent on NF-κB.

A20/TNFAIP3 的突变和多态性与各种炎症性疾病有关。然而,除了在炎症中发挥众所周知的作用外,A20 还能控制 EDAR 和 NF-κB 受体激活剂(RANK)诱导的 NF-κB 信号传导,分别调节表皮皮肤附属物和骨骼的发育。此外,A20 还通过一种依赖于 NF-κB 的机制来调节突触重塑。
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引用次数: 0
Tumor-initiating cells establish a niche to overcome isolation stress. 诱发肿瘤的细胞建立了一个生态位,以克服隔离压力。
IF 19 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-05-01 Epub Date: 2023-08-26 DOI: 10.1016/j.tcb.2023.08.001
Chengsheng Wu, Sara M Weis, David A Cheresh

While the tumor microenvironment is a critical contributor to cancer progression, early steps of tumor initiation and metastasis also rely on the ability of individual tumor cells to survive and thrive at locations where tumor stroma or immune infiltration has yet to be established. In this opinion article, we use the term 'isolation stress' to broadly describe the challenges that individual tumor cells must overcome during the initiation and expansion of the primary tumor beyond permissive boundaries and metastatic spread into distant sites, including a lack of cell-cell contact, adhesion to protumor extracellular matrix proteins, and access to nutrients, oxygen, and soluble factors that support growth. In particular, we highlight the ability of solitary tumor cells to autonomously generate a specialized fibronectin-enriched extracellular matrix to create their own pericellular niche that supports tumor initiation. Cancer cells that can creatively evade the effects of isolation stress not only become more broadly stress tolerant, they also tend to show enhanced stemness, drug resistance, tumor initiation, and metastasis.

虽然肿瘤微环境是癌症进展的关键因素,但肿瘤发生和转移的早期步骤也依赖于单个肿瘤细胞在肿瘤基质或免疫浸润尚未建立的位置生存和生长的能力。在这篇观点文章中,我们使用 "隔离压力 "一词来广义地描述单个肿瘤细胞在原发肿瘤的起始和扩展过程中必须克服的挑战,包括缺乏细胞间的接触、与原发肿瘤细胞外基质蛋白的粘附以及获得营养、氧气和支持生长的可溶性因子。我们特别强调了单个肿瘤细胞自主生成富含纤维连接蛋白的特化细胞外基质的能力,以创建自己的细胞外基质,支持肿瘤的发生。能够创造性地规避隔离应激影响的癌细胞不仅具有更广泛的应激耐受性,而且还倾向于表现出更强的干性、耐药性、肿瘤萌发和转移能力。
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引用次数: 0
Spermidine - an old molecule with a new age-defying immune function. 抹茶苷--一种古老的分子,却具有新的抗衰老免疫功能。
IF 19 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-05-01 Epub Date: 2023-09-16 DOI: 10.1016/j.tcb.2023.08.002
Kenji Chamoto, Baihao Zhang, Masaki Tajima, Tasuku Honjo, Sidonia Fagarasan

Polyamines - putrescine, spermidine, and spermine - are widely distributed aliphatic compounds known to regulate important biological processes in prokaryotic and eukaryotic cells. Therefore, spermidine insufficiency is associated with various physio-pathological processes, such as aging and cancers. Recent advances in immuno-metabolism and immunotherapy shed new light on the role of spermidine in immune cell regulation and anticancer responses. Here, we review novel works demonstrating that spermidine is produced by collective metabolic pathways of gut bacteria, bacteria-host co-metabolism, and by the host cells, including activated immune cells. We highlight the effectiveness of spermidine in enhancing antitumor responses in aged animals otherwise nonresponsive to immune checkpoint therapy and propose that spermidine supplementation could be used to enhance the efficacy of anti-PD-1 treatment.

多胺--腐胺、亚精胺和精胺--是分布广泛的脂肪族化合物,已知可调节原核细胞和真核细胞中的重要生物过程。因此,精胺不足与衰老和癌症等各种生理病理过程有关。免疫代谢和免疫疗法方面的最新进展使人们对亚精胺在免疫细胞调节和抗癌反应中的作用有了新的认识。在此,我们回顾了一些新的研究成果,这些成果表明,亚精胺是由肠道细菌的集体代谢途径、细菌-宿主协同代谢以及宿主细胞(包括活化的免疫细胞)产生的。我们强调了亚精胺在增强对免疫检查点疗法无反应的老年动物的抗肿瘤反应方面的有效性,并提出补充亚精胺可用于增强抗 PD-1 治疗的疗效。
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引用次数: 0
Cilia as Wnt signaling organelles 作为 Wnt 信号细胞器的纤毛
IF 19 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-05-01 DOI: 10.1016/j.tcb.2024.04.001
Christof Niehrs, Fabio Da Silva, Carina Seidl

Cilia and Wnt signaling have a complex relationship, wherein Wnt regulates cilia and, conversely, cilia may affect Wnt signaling. Recently, it was shown that Wnt receptors are present in flagella, primary cilia, and multicilia, where they transmit an intraciliary signal that is independent of β-catenin. Intraciliary Wnt signaling promotes ciliogenesis, affecting male fertility, adipogenesis, and mucociliary clearance. Wnt also stimulates the beating of motile cilia, highlighting that these nanomotors, too, are chemosensory. Intraciliary Wnt signaling employs a Wnt–protein phosphatase 1 (PP1) signaling axis, involving the canonical Wnt pathway’s inhibition of glycogen synthase kinase 3 (GSK3) to repress PP1 activity. Collectively, these findings support that cilia are Wnt signaling organelles, with implications for ciliopathies and cancer.

纤毛和 Wnt 信号传导之间的关系十分复杂,Wnt 可调控纤毛,反之,纤毛也可能影响 Wnt 信号传导。最近的研究表明,Wnt受体存在于鞭毛、初级纤毛和多纤毛中,它们在纤毛内传递独立于β-catenin的信号。纤毛内的 Wnt 信号可促进纤毛的生成,影响男性的生育能力、脂肪生成和粘液纤毛清除。Wnt 还能刺激运动纤毛的跳动,这表明这些纳米马达也具有化学感应能力。纤毛内的 Wnt 信号通过 Wnt 蛋白磷酸酶 1(PP1)信号轴传递,其中包括典型 Wnt 通路对糖原合酶激酶 3(GSK3)的抑制,从而抑制 PP1 的活性。总之,这些研究结果支持纤毛是Wnt信号细胞器,对纤毛疾病和癌症具有重要意义。
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引用次数: 0
How to enjoy and thrive in graduate school. 如何在研究生院享受快乐并茁壮成长。
IF 13 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-05-01 Epub Date: 2024-02-23 DOI: 10.1016/j.tcb.2024.02.003
Ramanujan S Hegde

Scientific research is an exploration of the unknown. The process is full of uncertainty, missteps, delightful surprises, painful lessons, and ultimately a measure of insight into nature. In this Science and Society article I suggest a few practical strategies that helped me navigate these challenges at the earliest stages of becoming a cell biologist.

科学研究是对未知的探索。这个过程充满了不确定性、失误、惊喜、痛苦的教训,以及最终对自然的洞察力。在这篇《科学与社会》(Science and Society)的文章中,我提出了一些实用的策略,帮助我在成为细胞生物学家的最初阶段应对这些挑战。
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引用次数: 0
The emerging role of receptor tyrosine kinase phase separation in cancer. 受体酪氨酸激酶相分离在癌症中的新作用。
IF 13 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-05-01 Epub Date: 2023-09-28 DOI: 10.1016/j.tcb.2023.09.002
Chi-Chuan Lin, Kin Man Suen, Jessica Lidster, John E Ladbury

Receptor tyrosine kinase (RTK)-mediated signal transduction is fundamental to cell function and drives important cellular outcomes which, when dysregulated, can lead to malignant tumour growth and metastasis. The initiation of signals from plasma membrane-bound RTKs is subjected to multiple regulatory mechanisms that control downstream effector protein recruitment and function. The high propensity of RTKs to condense via liquid-liquid phase separation (LLPS) into membraneless organelles with downstream effector proteins provides a further fundamental mechanism for signal regulation. Herein we highlight how this phenomenon contributes to cancer signalling and consider the potential impact of LLPS on outcomes for cancer patients.

受体酪氨酸激酶(RTK)介导的信号转导是细胞功能的基础,并驱动重要的细胞结果,当失调时,可导致恶性肿瘤生长和转移。来自质膜结合的RTKs的信号的启动受到控制下游效应蛋白募集和功能的多种调节机制的影响。RTK通过液-液相分离(LLPS)浓缩成具有下游效应蛋白的无膜细胞器的高倾向性为信号调节提供了进一步的基本机制。在此,我们强调了这一现象如何促进癌症信号传导,并考虑了LLPS对癌症患者预后的潜在影响。
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引用次数: 0
The ubiquitous role of ubiquitination in lipid metabolism. 泛素化在脂质代谢中的普遍作用。
IF 13 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-05-01 Epub Date: 2023-09-26 DOI: 10.1016/j.tcb.2023.09.001
Melanie Loix, Noam Zelcer, Jeroen F J Bogie, Jerome J A Hendriks

Lipids are essential molecules that play key roles in cell physiology by serving as structural components, for storage of energy, and in signal transduction. Hence, efficient regulation and maintenance of lipid homeostasis are crucial for normal cellular and tissue function. In the past decade, increasing research has shown the importance of ubiquitination in regulating the stability of key players in different aspects of lipid metabolism. This review describes recent insights into the regulation of lipid metabolism by ubiquitin signaling, discusses how ubiquitination can be targeted in diseases characterized by lipid dysregulation, and identifies areas that require further research.

脂质是在细胞生理学中发挥关键作用的重要分子,作为结构成分,用于储存能量和信号转导。因此,脂质稳态的有效调节和维持对正常的细胞和组织功能至关重要。在过去的十年里,越来越多的研究表明,泛素化在调节脂质代谢不同方面关键参与者的稳定性方面具有重要意义。这篇综述描述了泛素信号对脂质代谢调节的最新见解,讨论了泛素化如何在以脂质失调为特征的疾病中被靶向,并确定了需要进一步研究的领域。
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引用次数: 0
期刊
Trends in Cell Biology
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