Mechanisms of the epithelial-mesenchymal transition by TGF-beta.
Mechanisms of the epithelial-mesenchymal transition by TGF-beta.
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DOI：
10.2217/fon.09.90
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发表时间：
2009-10
期刊：
影响因子：
--
通讯作者：
Schiemann WP
中科院分区：
文献类型：
--
作者：
Wendt MK;Allington TM;Schiemann WP
上皮细胞屏障的形成源于干细胞向特化和极化上皮的限定的时空分化，这一过程称为间充质-上皮转变。相反的过程，上皮-间充质转化（EMT），是一个亚稳态的过程，使极化上皮细胞获得一个能动的成纤维细胞样表型。生理EMT也在促进组织愈合、重塑或修复以响应各种病理损伤中起重要作用。另一方面，病理生理EMT是介导局部癌获得转移表型的关键步骤。虽然转移显然是癌症最致命的方面，但我们对控制其发展的分子事件（包括潜在的EMT）的了解仍然相对不明确。转化生长因子-β（TGF-β）是一种多功能细胞因子，其监督和指导细胞发育、分化和稳态的所有方面，以及抑制它们不受控制的增殖和转化。相当二分法地，肿瘤发生颠覆了TGF-β的肿瘤抑制功能，并且在这样做时，将TGF-β转化为刺激病理生理学EMT和转移的肿瘤促进剂。因此，确定TGF-β如何在肿瘤发展中诱导EMT将使科学和医学能够产生能够阻止其这样做的能力的新型药理学试剂，从而改善癌症患者的临床过程。本文综述了TGF-β刺激正常和恶性细胞EMT的细胞、分子和微环境机制。
The formation of epithelial cell barriers results from the defined spatiotemporal differentiation of stem cells into a specialized and polarized epithelium, a process termed mesenchymal-epithelial transition. The reverse process, epithelial-mesenchymal transition (EMT), is a metastable process that enables polarized epithelial cells acquire a motile fibroblastoid phenotype. Physiological EMT also plays an essential role in promoting tissue healing, remodeling, or repair in response to a variety of pathological insults. On the other hand, pathophysiological EMT is a critical step in mediating the acquisition of metastatic phenotypes by localized carcinomas. Although metastasis clearly is the most lethal aspect of cancer, our knowledge of the molecular events that govern its development, including those underlying EMT, remain relatively undefined. Transforming growth factor-β (TGF-β) is a multifunctional cytokine that oversees and directs all aspects of cell development, differentiation, and homeostasis, as well as suppresses their uncontrolled proliferation and transformation. Quite dichotomously, tumorigenesis subverts the tumor suppressing function of TGF-β, and in doing so, converts TGF-β to a tumor promoter that stimulates pathophysiological EMT and metastasis. It therefore stands to reason that determining how TGF-β induces EMT in developing neoplasms will enable science and medicine to produce novel pharmacological agents capable of preventing its ability to do so, thereby improving the clinical course of cancer patients. Here we review the cellular, molecular, and microenvironmental mechanisms used by TGF-β to mediate its stimulation of EMT in normal and malignant cells.
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DOI：
10.1196/annals.1386.024
发表时间：
2006-01-01
期刊：
ESTROGENS AND HUMAN DISEASES
影响因子：
--
作者：
Buck, Miriam B.;Knabbe, Cornelius
通讯作者：
Knabbe, Cornelius
DOI：
10.1073/pnas.92.8.3239
发表时间：
1995-04-11
影响因子：
11.1
作者：
ALEXANDROW, MG;KAWABATA, M;MOSES, HL
通讯作者：
MOSES, HL
影响因子：
3.7
作者：
Azuma, M;Motegi, K;Sato, M
通讯作者：
Sato, M
影响因子：
15.9
作者：
Bates, RC;Bellovin, DI;Mercurio, AM
通讯作者：
Mercurio, AM
影响因子：
64.5
作者：
Bromberg, JF;Wrzeszczynska, MH;Darnell, JE
通讯作者：
Darnell, JE