Epithelial-mesenchymal transition and tumour invasion
Epithelial-mesenchymal transition and tumour invasion
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DOI：
10.1016/j.biocel.2007.07.011
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发表时间：
2007-01-01
影响因子：
4
通讯作者：
Guarino, Marcello
中科院分区：
文献类型：
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作者：
Guarino, Marcello
癌的侵袭意味着远处转移的可能性，但是，尽管它的临床重要性，它仍然是一个知之甚少的过程。越来越多的证据表明上皮-间质转化的作用，肿瘤细胞将削弱E-钙粘蛋白依赖的细胞间粘附;并增强运动性，从而能够渗透到周围组织中。在推进肿瘤前沿的激活的组织微环境似乎为触发这种变化提供了适当的刺激。生长因子和细胞外基质分子与肿瘤细胞膜受体的结合产生级联的细胞内信号，其可最终促进E-钙粘蛋白的下调和细胞骨架的激活。因此，细胞失去细胞间连接，并发出细胞质延伸，从基底表面通过基底膜的中断突出到基质隔室中。这些突起与间质基质建立新的接触，最后，细胞骨架的收缩允许细胞移位到基质中。在这里，空间和时间协调的扩张和收缩事件的重复循环确保了入侵细胞的运动。侵袭预示着产生转移的能力，因此上皮-间质转化可以为这一有害过程的机制提供新的见解。此外，由于已知参与上皮-间充质转化的失调蛋白似乎与癌症进展相关，因此它们可能被用作预后标志物或治疗靶点。因此，除了增加我们对肿瘤侵袭生物学的了解外，研究上皮-间充质转化将在未来为确定临床参数和药物治疗提供新的机会。(C)2007爱思唯尔有限公司保留所有权利。
Carcinoma invasion implies potentiality to metastasize distantly but, despite its clinical importance, it is still a poorly understood process. There is increasing evidence pointing to a role of epithelial-mesenchymal transition by which tumour cells would weaken E-cadherin-dependent intercellular adhesion; and enhance motility, thus becoming able to penetrate into surrounding tissues. The activated tissue microenvironment at the advancing tumour front seems to provide the appropriate stimuli for triggering this change. The binding of growth factors and extracellular matrix molecules to tumour cell membrane receptors generates cascades of intracellular signals that could ultimately promote the down-regulation of E-cadherin and the activation of the cytoskeleton. Therefore, cells lose intercellular junctions and emanate cytoplasmic extensions that protrude from the basal surface into the stromal compartment through interruptions of the basement membrane. These protrusions establish new contacts with the interstitial matrix and, finally, the contraction of the cytoskeleton allows cell translocation into the stroma. Here, repeated cycles of spatially and temporally coordinated protrusive and contractile events ensure the locomotion of invading cells. Invasion predicts the ability to generate metastasis, therefore epithelial-mesenchymal transition could provide new insights on the mechanisms underlying this detrimental process. Furthermore, since deregulated proteins known to be involved in epithelial-mesenchymal transition seem associated with cancer progression, they could potentially be utilized as prognostic markers or therapeutic targets. Thus, in addition to increasing our knowledge of tumour invasion biology, studying epithelial-mesenchymal transition will, in the future, offer novel opportunities to define clinical parameters and pharmacological treatment. (C) 2007 Elsevier Ltd. All rights reserved.