Epithelial-mesenchymal transition, the tumor microenvironment, and metastatic behavior of epithelial malignancies.
Epithelial-mesenchymal transition, the tumor microenvironment, and metastatic behavior of epithelial malignancies.
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发表时间：
2012
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通讯作者：
L. Talbot;S. Bhattacharya;P. Kuo
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作者：
L. Talbot;S. Bhattacharya;P. Kuo
目的近年来对肿瘤转移机制的研究越来越深入，为预防肿瘤转移提供了重要的治疗靶点。我们试图回顾上皮-间质转化和肿瘤微环境对癌症转移的贡献。上皮-间质转化是上皮细胞失去细胞间连接和基底-根尖极性，获得可塑性、移动性、侵袭能力、茎样特征和抗凋亡能力的过程。这个细胞生物学程序在胚胎学、伤口愈合和肿瘤转移病理学中都很活跃，并且与肿瘤微环境的机械和细胞成分一起，为上皮恶性肿瘤获得转移能力提供了关键的动力。方法利用PubMed检索“上皮-间质转化”、“肿瘤微环境”、“TGF-β与癌症”、“Wnt与上皮-间质转化”、“Notch与上皮-间质转化”、“Hedgehog与上皮-间质转化”、“缺氧与转移”等相关文献。对相关的初步研究和综述文章进行了评估。结果参与上皮-间质转化的主要信号通路包括TGF-β、Wnt、Notch、Hedgehog等。这些途径汇聚在几个转录因子上，包括锌指蛋白Snail and Slug、Twist、ZEB 1/2和Smads。这些因子相互作用，提供相关信号通路之间的串扰。MicroRNA的抑制和表观遗传变化也影响上皮-间质转化过程中的变化。肿瘤微环境的细胞和机械成分也是决定转移潜力的关键因素。结论：虽然促进肿瘤转移的机制非常广泛且仍在深入研究中，但上皮-间质转化程序和肿瘤微环境都在转移潜能的获得中起关键作用。随着我们对这些复杂性的理解的增加，靶向治疗这些过程的能力将为上皮恶性肿瘤和转移的治疗提供新的希望。
OBJECTIVE The mechanisms of cancer metastasis have been intensely studied recently and may provide vital therapeutic targets for metastasis prevention. We sought to review the contribution of epithelial-mesenchymal transition and the tumor microenvironment to cancer metastasis. SUMMARY BACKGROUND DATA Epithelial-mesenchymal transition is the process by which epithelial cells lose cell-cell junctions and baso-apical polarity and acquire plasticity, mobility, invasive capacity, stemlike characteristics, and resistance to apoptosis. This cell biology program is active in embryology, wound healing, and pathologically in cancer metastasis, and along with the mechanical and cellular components of the tumor microenvironment, provides critical impetus for epithelial malignancies to acquire metastatic capability. METHODS A literature review was performed using PubMed for "epithelial-mesenchymal transition", "tumor microenvironment", "TGF-β and cancer", "Wnt and epithelial-mesenchymal transition", "Notch and epithelial-mesenchymal transition", "Hedgehog and epithelial-mesenchymal transition" and "hypoxia and metastasis". Relevant primary studies and review articles were assessed. RESULTS Major signaling pathways involved in epithelial-mesenchymal transition include TGF-β, Wnt, Notch, Hedgehog, and others. These pathways converge on several transcription factors, including zinc finger proteins Snail and Slug, Twist, ZEB 1/2, and Smads. These factors interact with one another and others to provide crosstalk between the relevant signaling pathways. MicroRNA suppression and epigenetic changes also influence the changes involved in epithelial-mesenchymal transition. Cellular and mechanical components of the tumor microenvironment are also critical in determining metastatic potential. CONCLUSIONS While the mechanisms promoting metastasis are extremely wide ranging and still under intense investigation, the epithelial-mesenchymal transition program and the tumor microenvironment are both critically involved in the acquisition of metastatic potential. As our understanding of these complexities increases, the ability to target these processes for therapy will offer new promise in the treatment of epithelial malignancy and metastasis.