Appropriate mechanical forces on cells are vital for normal cell behaviour and this review discusses the possibility that tumour initiation depends partly on the disruption of the normal physical architecture of the extracellular matrix (ECM) around a cell. The alterations that occur thence promote oncogene expression. Some questions, that are not answered with certainty by current consensus mechanisms of tumourigenesis, are elegantly explained by the triggering of tumours being a property of the physical characteristics of the ECM, which is operative following loading of the tumour initiation process with a relevant gene variant. Clinical observations are consistent with this alternative hypothesis which is derived from studies that have, together, accumulated an extensive variety of data incorporating biochemical, genetic and clinical findings. Thus, this review provides support for the view that the ECM may have an executive function in induction of a tumour. Overall, reported observations suggest that either restoring an ECM associated with homeostasis or targeting the related signal transduction mechanisms may possibly be utilised to modify or control the early progression of cancers. The review provides a coherent template for discussing the notion, in the context of contemporary knowledge, that tumourigenesis is an alliance of biochemistry, genetics and biophysics, in which the physical architecture of the ECM may be a fundamental component. For more definitive clarification of the concept there needs to be a phalanx of experiments conceived around direct questions that are raised by this paper.

中文翻译：

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肿瘤发生：关于“负载触发”机制证据的讨论。

细胞上适当的机械力对于正常细胞行为至关重要，这篇综述讨论了肿瘤发生部分取决于细胞周围细胞外基质（ECM）正常物理结构破坏的可能性。由此发生的改变促进癌基因表达。目前肿瘤发生的共识机制尚未明确回答一些问题，但肿瘤的触发是 ECM 物理特性的一个属性，ECM 在加载相关基因变体后在肿瘤启动过程中发挥作用，从而得到了很好的解释。 。临床观察结果与这一替代假设相一致，该假设源自研究，这些研究共同积累了广泛的各种数据，包括生化、遗传和临床发现。因此，本综述支持了 ECM 可能在肿瘤诱导中具有执行功能的观点。总体而言，报告的观察结果表明，恢复与稳态相关的 ECM 或针对相关信号转导机制可能可用于改变或控制癌症的早期进展。该综述为在当代知识背景下讨论这一概念提供了一个连贯的模板，即肿瘤发生是生物化学、遗传学和生物物理学的结合，其中 ECM 的物理结构可能是一个基本组成部分。为了更明确地澄清这个概念，需要围绕本文提出的直接问题进行一系列实验。