The Dual Role of TGFβ in Human Cancer: From Tumor Suppression to Cancer Metastasis.
The Dual Role of TGFβ in Human Cancer: From Tumor Suppression to Cancer Metastasis.
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DOI：
10.5402/2012/381428
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Lebrun JJ
中科院分区：
文献类型：
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作者：
Lebrun JJ
tgf - β转化生长因子（tgf - β）超家族包含广泛且进化保守的多肽生长因子，可调节和协调所有细胞类型和组织的生长和分化。TGFβ家族成员在早期发育和胚胎发生过程中调节不对称细胞分裂和细胞命运决定，同时在成年期的激素和免疫反应、细胞生长、细胞死亡和细胞永生、骨形成、组织重塑和修复以及红细胞生成中发挥主要调节作用。tgf - β是该家族的创始成员，其生物学和生理功能及其受体对人类疾病，特别是癌症至关重要。通过调节细胞生长、死亡和永生，TGFβ信号通路在正常细胞和早期癌中发挥肿瘤抑制作用。因此，大量的人类肿瘤是由于编码各种tgf - β信号成分的基因突变或缺失而产生的，这并不奇怪。随着肿瘤的发展和进展，tgf - β的这些保护和细胞抑制作用往往会丧失。然后tgf - β信号转换促进癌症进展、侵袭和肿瘤转移。本文将深入讨论tgf - β在人类癌症中的双重作用的分子机制，并强调开发新的治疗策略的挑战和重要性，这些策略专门针对阻断tgf - β信号通路的前转移臂而不影响其肿瘤抑制作用。
The transforming growth factor-beta (TGFβ) superfamily encompasses widespread and evolutionarily conserved polypeptide growth factors that regulate and orchestrate growth and differentiation in all cell types and tissues. While they regulate asymmetric cell division and cell fate determination during early development and embryogenesis, TGFβ family members play a major regulatory role in hormonal and immune responses, cell growth, cell death and cell immortalization, bone formation, tissue remodeling and repair, and erythropoiesis throughout adult life. The biological and physiological functions of TGFβ, the founding member of this family, and its receptors are of central importance to human diseases, particularly cancer. By regulating cell growth, death, and immortalization, TGFβ signaling pathways exert tumor suppressor effects in normal cells and early carcinomas. Thus, it is not surprising that a high number of human tumors arise due to mutations or deletions in the genes coding for the various TGFβ signaling components. As tumors develop and progress, these protective and cytostatic effects of TGFβ are often lost. TGFβ signaling then switches to promote cancer progression, invasion, and tumor metastasis. The molecular mechanisms underlying this dual role of TGFβ in human cancer will be discussed in depth in this paper, and it will highlight the challenge and importance of developing novel therapeutic strategies specifically aimed at blocking the prometastatic arm of the TGFβ signaling pathway without affecting its tumor suppressive effects.