Department of Anatomy & Cell Biology, The Schulich School of Medicine and Dentistry, Western University, 438 Medical Science Building, London, ON, N6A 5C1, Canada.
J Cell Commun Signal. 2012 Dec;6(4):233-48. doi: 10.1007/s12079-012-0179-x. Epub 2012 Oct 9.
The microenvironment acts as a conduit for cellular communication, delivering signals that direct development and sustain tissue homeostasis. In pathologies such as cancer, this integral function of the microenvironment is hijacked to support tumor growth and progression. Cells sense the microenvironment via signal transduction pathways culminating in altered gene expression. In addition to induced transcriptional changes, the microenvironment exerts its effect on the cell through regulation of post-transcriptional processes including alternative splicing and translational control. Here we describe how alternative splicing and protein translation are controlled by microenvironmental parameters such as oxygen availability. We also emphasize how these pathways can be utilized to support processes that are hallmarks of cancer such as angiogenesis, proliferation, and cell migration. We stress that cancer cells respond to their microenvironment through an integrated regulation of gene expression at multiple levels that collectively contribute to disease progression.
微环境充当细胞通讯的渠道，传递信号，指导发育并维持组织内稳态。在癌症等疾病中，微环境的这一重要功能被劫持，以支持肿瘤生长和进展。细胞通过信号转导途径感知微环境，最终导致基因表达的改变。除了诱导的转录变化外，微环境还通过调节包括选择性剪接和翻译控制在内的转录后过程对细胞施加影响。在这里，我们描述了微环境参数（如氧可用性）如何控制选择性剪接和蛋白质翻译。我们还强调了如何利用这些途径来支持癌症的标志性过程，如血管生成、增殖和细胞迁移。我们强调，癌细胞通过在多个水平上整合基因表达的调节来对微环境做出反应，这些反应共同导致疾病的进展。
