Tumor-promoting functions of transforming growth factor-β in progression of cancer.
Tumor-promoting functions of transforming growth factor-β in progression of cancer.
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DOI：
10.3109/03009734.2011.638729
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发表时间：
2012-05
影响因子：
3.4
通讯作者：
Koinuma D
中科院分区：
文献类型：
--
作者：
Miyazono K;Ehata S;Koinuma D
转化生长因子-β (TGF-β)在癌症进展过程中具有肿瘤抑制和肿瘤促进功能。在这里，我们描述了TGF-β的促肿瘤功能以及这些功能如何在癌症进展中发挥作用。正常上皮细胞通过TGF-β的作用发生上皮-间充质转化（epithelial-mesenchymal transition， EMT），而TGF-β和成纤维细胞生长因子（fibroblast growth factor， FGF）-2的作用可使其转分化为活化的成纤维细胞，并具有高度的迁移性，从而促进肿瘤的侵袭和转移。TGF-β还可诱导肿瘤细胞内的EMT， EMT可受致瘤和抑瘤信号调控。除了EMT促进外，TGF-β还通过调节细胞存活、血管生成、血管完整性以及与肿瘤微环境的相互作用等机制促进肿瘤的侵袭转移。TGF-β在调节某些类型细胞（包括胶质瘤起始细胞）的致癌特性中也起着关键作用。因此，这些发现可能有助于通过抑制TGF-β信号传导来建立晚期癌症的治疗策略。
Transforming growth factor-β (TGF-β) elicits both tumor-suppressive and tumor-promoting functions during cancer progression. Here, we describe the tumor-promoting functions of TGF-β and how these functions play a role in cancer progression. Normal epithelial cells undergo epithelial-mesenchymal transition (EMT) through the action of TGF-β, while treatment with TGF-β and fibroblast growth factor (FGF)-2 results in transdifferentiation into activated fibroblastic cells that are highly migratory, thereby facilitating cancer invasion and metastasis. TGF-β also induces EMT in tumor cells, which can be regulated by oncogenic and anti-oncogenic signals. In addition to EMT promotion, invasion and metastasis of cancer are facilitated by TGF-β through other mechanisms, such as regulation of cell survival, angiogenesis, and vascular integrity, and interaction with the tumor microenvironment. TGF-β also plays a critical role in regulating the cancer-initiating properties of certain types of cells, including glioma-initiating cells. These findings thus may be useful for establishing treatment strategies for advanced cancer by inhibiting TGF-β signaling.