The TGF-beta paradox in human cancer: an update.
The TGF-beta paradox in human cancer: an update.
复制标题
DOI：
10.2217/14796694.5.2.259
复制
发表时间：
2009-03
期刊：
影响因子：
--
通讯作者：
Schiemann WP
中科院分区：
文献类型：
--
作者：
Tian M;Schiemann WP
转化生长因子-β (TGF-β)通过诱导细胞周期阻滞、分化、凋亡和保持基因组稳定性，在维持组织稳态中发挥重要作用。因此，TGF-β是一种有效的抗癌药物，可以阻止上皮细胞、内皮细胞和造血细胞不受控制的增殖。有趣的是，肿瘤发生通常会引起TGF-β信号通路的畸变，从而产生对TGF-β细胞抑制活性的抗性，从而促进人类恶性肿瘤的发生和进展。此外，这些遗传和表观遗传事件共同作用，将TGF-β从肿瘤形成的抑制因子转化为肿瘤生长、侵袭和转移的促进因子。TGF-β在肿瘤发生过程中的二分性被称为“TGF-β悖论”，这仍然是关于这种多功能细胞因子的生理病理作用的最关键和最神秘的问题。在这里，我们回顾了直接影响我们对“TGF-β悖论”的理解的最新发现，并讨论了它们对靶向TGF-β在肿瘤发生和进展中的致癌活性的重要性。
Transforming growth factor-β (TGF-β) plays an essential role in maintaining tissue homeostasis through its ability to induce cell cycle arrest, differentiation, apoptosis, and to preserve genomic stability. Thus, TGF-β is a potent anticancer agent that prohibits the uncontrolled proliferation of epithelial, endothelial, and hematopoietic cells. Interestingly, tumorigenesis typically elicits aberrations in the TGF-β signaling pathway that engenders resistance to the cytostatic activities of TGF-β, thereby enhancing the development and progression of human malignances. Moreover, these genetic and epigenetic events conspire to convert TGF-β from a suppressor of tumor formation to a promoter of their growth, invasion, and metastasis. The dichotomous nature of TGF-β during tumorigenesis is known as the “TGF-β Paradox,” which remains the most critical and mysterious question concerning the physiopathological role of this multifunctional cytokine. Here we review recent findings that directly impact our understanding of the “TGF-β Paradox” and discuss their importance to targeting the oncogenic activities of TGF-β in developing and progressing neoplasms.