State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, 100084, China.
Sci China Life Sci. 2017 Oct;60(10):1133-1141. doi: 10.1007/s11427-017-9173-5. Epub 2017 Oct 23.
Transforming growth factor-β (TGF-β) signaling regulates cell proliferation, differentiation, migration and death, and plays a critical role in embryogenesis and tissue homeostasis. Its deregulation results in various diseases including tumor formation. Receptor tyrosine kinases (RTKs), such as epidermal growth factor receptor (EGFR), fibroblast growth factor receptor (FGFR), vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR), also play key roles in the development and progression of many types of tumors. It has been realized that TGF-β signaling and RTK pathways interact with each other and their interplay is important for cancer development. They are mutually regulated and cooperatively modulate cell survival and migration, epithelial-mesenchymal transition, and tumor microenvironment to accelerate tumorigenesis and tumor metastasis. RTKs can modulate Smad-dependent transcription or cooperate with TGF-β to potentiate its oncogenic activity, while TGF-β signaling can in turn control RTK signaling by regulating their activities or expression. This review summarizes current understandings of the interplay between TGF-β signaling and RTKs and its influence on tumor development.
转化生长因子-β（TGF-β）信号通路调节细胞增殖、分化、迁移和死亡，在胚胎发生和组织稳态中发挥关键作用。其失调会导致包括肿瘤形成在内的各种疾病。受体酪氨酸激酶（RTKs），如表皮生长因子受体（EGFR）、成纤维细胞生长因子受体（FGFR）、血管内皮生长因子受体（VEGFR）和血小板衍生生长因子受体（PDGFR），也在多种类型肿瘤的发生和发展中发挥关键作用。已经意识到 TGF-β信号通路和 RTK 途径相互作用，它们的相互作用对于癌症的发展很重要。它们相互调节，并协同调节细胞存活和迁移、上皮-间充质转化和肿瘤微环境，以加速肿瘤发生和肿瘤转移。RTKs 可以调节 Smad 依赖性转录或与 TGF-β合作增强其致癌活性，而 TGF-β信号通路可以通过调节它们的活性或表达来反过来控制 RTK 信号通路。本综述总结了目前对 TGF-β信号通路和 RTKs 相互作用及其对肿瘤发生影响的理解。
