The network of epithelial-mesenchymal transition: potential new targets for tumor resistance.
The network of epithelial-mesenchymal transition: potential new targets for tumor resistance.
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DOI：
10.1007/s00432-014-1840-y
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发表时间：
2015-10
影响因子：
3.6
通讯作者：
Li JJ
中科院分区：
文献类型：
--
作者：
Nantajit D;Lin D;Li JJ
在多细胞后生动物中，极化的上皮细胞转变为可移动的间充质细胞以迁移到另一个位置的能力由一种独特的过程控制，称为上皮-间充质转化(EMT)。虽然EMT是正常组织和器官发育所必需的细胞可塑性过程，但它参与了一系列肿瘤细胞的恶性表型，包括增殖和侵袭、血管生成、癌细胞的干性和对化疗放疗的抵抗。尽管EMT被广泛研究并被证明在肿瘤转移和维持肿瘤特征方面发挥关键作用，但对整个EMT信号网络缺乏清晰的图景，动摇了针对EMT的潜在临床试验。在这篇综述中，我们强调了EMT与肿瘤侵袭性、低氧、血管生成和肿瘤干细胞相关的潜在关键治疗靶点，强调了与EMT相关的NF-κB/HER2/STAT3通路在乳腺癌干细胞辐射抵抗中的作用。进一步定义由于EMT控制的肿瘤微环境导致的肿瘤干细胞再繁殖，将有助于理解肿瘤如何利用EMT机制获得其生存和扩张优势。对EMT的认识将为治疗耐药转移灶的临床试验提供更有效的靶点。
In multiple cell metazoans, the ability of polarized epithelial cells to convert to motile mesenchymal cells in order to relocate to another location is governed by a unique process termed epithelial-mesenchymal transition (EMT). While being an essential process of cellular plasticity for normal tissue and organ developments, EMT is found to be involved in an array of malignant phenotypes of tumor cells including proliferation and invasion, angiogenesis, stemness of cancer cells and resistance to chemo-radiotherapy. Although EMT is being extensively studied and demonstrated to play a key role in tumor metastasis and in sustaining tumor hallmarks, there is a lack of clear picture of the overall EMT signaling network, wavering the potential clinical trials targeting EMT. In this review, we highlight the potential key therapeutic targets of EMT linked with tumor aggressiveness, hypoxia, angiogenesis and cancer stem cells, emphasizing on an emerging EMT-associated NF-κB/HER2/STAT3 pathway in radioresistance of breast cancer stem cells. Further definition of cancer stem cell repopulation due to EMT-controlled tumor microenvironment will help to understand how tumors exploit the EMT mechanisms for their survival and expansion advantages. The knowledge of EMT will offer more effective targets in clinical trials to treat therapy-resistant metastatic lesions.