Spencer Virginia A, Xu Ren, Bissell Mina J
Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
Adv Cancer Res. 2007;97:275-94. doi: 10.1016/S0065-230X(06)97012-2.
Almost three decades ago, we presented a model where the extracellular matrix (ECM) was postulated to influence gene expression and tissue-specificity through the action of ECM receptors and the cytoskeleton. This hypothesis implied that ECM molecules could signal to the nucleus and that the unit of function in higher organisms was not the cell alone, but the cell plus its microenvironment. We now know that ECM invokes changes in tissue and organ architecture and that tissue, cell, nuclear, and chromatin structure are changed profoundly as a result of and during malignant progression. Whereas some evidence has been generated for a link between ECM-induced alterations in tissue architecture and changes in both nuclear and chromatin organization, the manner by which these changes actively induce or repress gene expression in normal and malignant cells is a topic in need of further attention. Here, we will discuss some key findings that may provide insights into mechanisms through which ECM could influence gene transcription and how tumor cells acquire the ability to overcome these levels of control.
大约三十年前，我们提出了一个模型，假定细胞外基质（ECM）通过ECM受体和细胞骨架的作用来影响基因表达和组织特异性。这一假说意味着ECM分子可以向细胞核发出信号，并且高等生物中的功能单位不仅仅是细胞本身，而是细胞及其微环境。我们现在知道，ECM会引起组织和器官结构的变化，并且在恶性进展过程中以及由于恶性进展，组织、细胞、细胞核和染色质结构会发生深刻改变。虽然已经有一些证据表明ECM诱导的组织结构改变与细胞核和染色质组织变化之间存在联系，但这些变化在正常细胞和恶性细胞中如何积极诱导或抑制基因表达仍是一个需要进一步关注的课题。在这里，我们将讨论一些关键发现，这些发现可能为ECM影响基因转录的机制以及肿瘤细胞如何获得克服这些调控水平的能力提供见解。
