文章：

TGFβ信号传导：癌症进展中的复杂网络

TGFβ signalling: a complex web in cancer progression

原文发布日期：2010-06-01

DOI: 10.1038/nrc2853

类型: Review Article

开放获取: 否

要点：

1. Transforming growth factor-β (TGFβ) signalling is mediated by TGFβ ligands, type 1 and type 2 receptors, and Smad proteins. TGFβ also regulates non-Smad pathways.
2. TGFβ stimulation inhibits cancer cell proliferation in some cellular contexts and promotes it in others. Numerous factors are involved in TGFβ-regulated cell proliferation and keep its signalling pathways balanced.
3. In addition to perturbation of TGFβ signalling, disruption or mutation of regulators of TGFβ signalling can lead to a loss of balanced TGFβ signalling, resulting in the generation and progression of tumours.
4. TGFβ signalling in cancer cells has dual roles in the regulation of cell death and proliferation.
5. TGFβ signalling has crucial roles in the maintenance of self-renewal and tumorigenic activity of glioma-initiating cells and leukaemia-initiating cells, whereas the function of TGFβ signalling in breast cancer-initiating cells is controversial.
6. TGFβ signalling is involved in several cell responses during cancer cell metastasis, and cell type-dependent and context-dependent factors contribute to the regulation of tumour metastasis.
7. The TGFβ pathway has been targeted for cancer therapy using multiple strategies. Some of them are currently in clinical trials.

要点翻译：

1. 转化生长因子-β（TGFβ）信号传导由TGFβ配体、1型和2型受体以及Smad蛋白介导。TGFβ同时调控非Smad信号通路。
2. 在不同细胞环境中，TGFβ刺激既能抑制癌细胞增殖，也能促进其增殖。多种因子参与TGFβ调控的细胞增殖过程，维持其信号通路平衡。
3. 除TGFβ信号传导紊乱外，其调控因子的破坏或突变也会导致TGFβ信号失衡，进而引发肿瘤的发生与发展。
4. 在癌细胞中，TGFβ信号对细胞死亡和增殖具有双重调控作用。
5. TGFβ信号在神经胶质瘤起始细胞和白血病起始细胞的自我更新与致瘤活性维持中起关键作用，而其对乳腺癌起始细胞的功能仍存争议。
6. 在癌细胞转移过程中，TGFβ信号参与多种细胞反应，肿瘤转移的调控受细胞类型依赖性及环境依赖性因素影响。
7. 目前已有多种靶向TGFβ通路的癌症治疗策略，其中部分方案正处于临床试验阶段。

英文摘要：

The distortion of growth factor signalling is the most important prerequisite in tumour progression. Transforming growth factor-β (TGFβ) signalling regulates tumour progression by a tumour cell-autonomous mechanism or through tumour–stroma interaction, and has either a tumour-suppressing or tumour-promoting function depending on cellular context. Such inherent complexity of TGFβ signalling results in arduous, but promising, assignments for developing therapeutic strategies against malignant tumours. As numerous cellular context-dependent factors tightly maintain the balance of TGFβ signalling and contribute to the regulation of TGFβ-induced cell responses, in this Review we discuss how they maintain the balance of TGFβ signalling and how their collapse leads to tumour progression.

摘要翻译： 

生长因子信号通路的异常是肿瘤进展最重要的前提。转化生长因子-β（TGFβ）信号通过肿瘤细胞自身机制或肿瘤-基质相互作用调控肿瘤进展，并根据细胞环境发挥抑瘤或促瘤功能。TGFβ信号的这种内在复杂性使得针对恶性肿瘤的治疗策略开发既艰巨又充满前景。由于众多依赖细胞环境的因素严密维持TGFβ信号的平衡并参与调控TGFβ诱导的细胞反应，本文将讨论它们如何维持TGFβ信号的平衡，以及这种平衡的崩溃如何导致肿瘤进展。

原文链接：

TGFβ signalling: a complex web in cancer progression