文章：

TGFβ：癌症的双重分子

TGFβ: the molecular Jekyll and Hyde of cancer

原文发布日期：2006-07-01

DOI: 10.1038/nrc1926

类型: Review Article

开放获取: 否

要点：

1. TGFβ signalling is tumour suppressive in epithelial cells, whereas it can promote invasion and metastasis during the later stages of carcinoma progression.
2. During tumour progression, tumour cells frequently lose the growth-inhibitory response to TGFβ, and this is associated with an increased expression of TGFβ in the microenvironment.
3. TGFβ-mediated regulation in the tumour microenvironment can be attributed to many factors, including those that involve cell-autonomous signalling, stromal–epithelial interactions, inflammation, immune evasion and angiogenesis.
4. Cell-autonomous TGFβ signalling can cause epithelial–mesenchymal transitions (EMT) in carcinoma cells, which increase invasion and metastasis.
5. Conversely, the abrogation of carcinoma-cell-autonomous TGFβ signalling can increase metastasis in the apparent absence of EMT.
6. Together, the cell-type-dependent and context-dependent effects of TGFβ signalling contribute to the regulation of tumour initiation, progression and metastasis.
7. Despite the complex nature of TGFβ-mediated regulatory signalling in the tumour microenvironment, many aspects of signalling through this pathway have been targeted for therapeutic intervention using systemic and cell-specific strategies, with some indications of efficacy.

要点翻译：

1. TGFβ信号通路上皮细胞中具有抑制肿瘤作用，但在癌变进展后期却能促进侵袭和转移。
2. 在肿瘤进展过程中，肿瘤细胞常丧失对TGFβ的生长抑制反应，这与微环境中TGFβ表达增加相关。
3. TGFβ在肿瘤微环境中的调控作用可归因于多种因素，包括细胞自主信号传导、基质-上皮相互作用、炎症反应、免疫逃逸及血管生成。
4. 细胞自主性TGFβ信号可诱导癌细胞发生上皮-间质转化（EMT），从而增强侵袭和转移能力。
5. 相反，在未见EMT发生的情况下，阻断癌细胞的自主性TGFβ信号传导反而可能促进转移。
6. TGFβ信号通路通过其细胞类型依赖性和环境依赖性的双重特性，共同调控肿瘤的发生、进展及转移过程。
7. 尽管TGFβ介导的调控信号在肿瘤微环境中具有复杂性，但通过全身性和细胞特异性治疗策略靶向该通路的多个环节已显现出一定疗效。

英文摘要：

Transforming growth factor-β (TGFβ) signalling regulates cancer through mechanisms that function either within the tumour cell itself or through host–tumour cell interactions. Studies of tumour-cell-autonomous TGFβ effects show clearly that TGFβ signalling has a mechanistic role in tumour suppression and tumour promotion. In addition, factors in the tumour microenvironment, such as fibroblasts, immune cells and the extracellular matrix, influence the ability of TGFβ to promote or suppress carcinoma progression and metastasis. The complex nature of TGFβ signalling and crosstalk in the tumour microenvironment presents a unique challenge, and an opportunity to develop therapeutic intervention strategies for targeting cancer.

摘要翻译： 

转化生长因子-β（TGFβ）信号通过作用于肿瘤细胞自身或宿主-肿瘤细胞相互作用调控癌症。对肿瘤细胞自主TGFβ效应的研究明确显示，TGFβ信号在肿瘤抑制和肿瘤促进中均具有机制性作用。此外，肿瘤微环境中的成纤维细胞、免疫细胞及细胞外基质等因素，也影响TGFβ促进或抑制癌进展与转移的能力。TGFβ信号在肿瘤微环境中的复杂性及其交互作用，既带来独特挑战，也提供了开发靶向癌症治疗干预策略的机遇。

原文链接：

TGFβ: the molecular Jekyll and Hyde of cancer