Translational Research Program, Vall d'Hebron Institute of Oncology, 08035 Barcelona, Spain.
Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain.
Cold Spring Harb Perspect Biol. 2017 Dec 1;9(12):a022277. doi: 10.1101/cshperspect.a022277.
Transforming growth factor-β (TGF-β) induces a pleiotropic pathway that is modulated by the cellular context and its integration with other signaling pathways. In cancer, the pleiotropic reaction to TGF-β leads to a diverse and varied set of gene responses that range from cytostatic and apoptotic tumor-suppressive ones in early stage tumors, to proliferative, invasive, angiogenic, and oncogenic ones in advanced cancer. Here, we review the knowledge accumulated about the molecular mechanisms involved in the dual response to TGF-β in cancer, and how tumor cells evolve to evade the tumor-suppressive responses of this signaling pathway and then hijack the signal, converting it into an oncogenic factor. Only through the detailed study of this complexity can the suitability of the TGF-β pathway as a therapeutic target against cancer be evaluated.
转化生长因子-β(TGF-β)诱导一种多效途径,该途径受细胞环境及其与其他信号通路的整合调节。在癌症中,TGF-β 的多效反应导致一系列不同的基因反应,从早期肿瘤中的细胞静止和凋亡性肿瘤抑制因子到晚期癌症中的增殖、侵袭、血管生成和致癌因子。在这里,我们回顾了关于癌症中 TGF-β 双重反应所涉及的分子机制的知识积累,以及肿瘤细胞如何进化以逃避这种信号通路的肿瘤抑制反应,然后劫持信号,将其转化为致癌因子。只有通过对这种复杂性的详细研究,才能评估 TGF-β 途径作为抗癌治疗靶点的适宜性。