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Abstract：
Contact inhibition (CI) represents a crucial tumor-suppressive mechanism responsible for controlling the unbridled growth of cells, thus preventing the formation of cancerous tissues. CI can be further categorized into two distinct yet interrelated components: CI of locomotion (CIL) and CI of proliferation (CIP). These two components of CI have historically been viewed as separate processes, but emerging research suggests that they may be regulated by both distinct and shared pathways. Specifically, recent studies have indicated that both CIP and CIL utilize mechanotransduction pathways, a process that involves cells sensing and responding to mechanical forces. This review article describes the role of mechanotransduction in CI, shedding light on how mechanical forces regulate CIL and CIP. Emphasis is placed on filamin A (FLNA)-mediated mechanotransduction, elucidating how FLNA senses mechanical forces and translates them into crucial biochemical signals that regulate cell locomotion and proliferation. In addition to FLNA, trans-acting factors (TAFs), which are proteins or regulatory RNAs capable of directly or indirectly binding to specific DNA sequences in distant genes to regulate gene expression, emerge as sensitive players in both the mechanotransduction and signaling pathways of CI. This article presents methods for identifying these TAF proteins and profiling the associated changes in chromatin structure, offering valuable insights into CI and other biological functions mediated by mechanotransduction. Finally, it addresses unanswered research questions in these fields and delineates their possible future directions.
摘要：
接触抑制（CI）代表了一个关键的肿瘤抑制机制，负责控制细胞的无限制生长，从而防止癌组织的形成。CI可以进一步分为两个不同但相互关联的组成部分：运动CI（CIL）和增殖CI（CIP）。CI的这两个组成部分历来被视为独立的过程，但是新兴的研究表明，它们可能受到不同的和共同的途径的调节。具体来说,最近的研究表明，CIP和CIL都利用机械转导途径，一个涉及细胞感知和响应机械力的过程。这篇综述文章描述了机械传导在CI中的作用，阐明了机械力如何调节CIL和CIP。重点放在丝状蛋白A（FLNA）介导的机械转导，阐明FLNA如何感知机械力并将其转化为调节细胞运动和增殖的关键生化信号。除了FLNA,反式作用因子(TAF)，它们是能够直接或间接地与远处基因中的特定DNA序列结合以调节基因表达的蛋白质或调节RNA，在CI的机械传导和信号传导途径中都是敏感的参与者。本文介绍了鉴定这些TAF蛋白和分析染色质结构相关变化的方法，为CI和机械转导介导的其他生物学功能提供有价值的见解。最后,它解决了这些领域尚未解决的研究问题，并描绘了它们可能的未来方向。
