Loss of cytostatic regulation by TGF-beta during EGFR-driven tumor development

生长因子和细胞因子信号网络控制着细胞行为的许多方面，如增殖、存活、迁移、侵袭能力、转化和分化。在正常细胞中，这些复杂的信号通路受到严格调控。这些信号的改变经常被发现直接或间接地引起肿瘤的形成。转化生长因子-b （TGF-b）和表皮生长因子（EGF）信号通路都是独立的肿瘤形成的关键调节因子，因此它们是潜在的治疗靶点。然而，尽管这两种途径已被广泛研究，但对TGF-b和EGF途径之间的串扰知之甚少。本项目将在egfr过表达肿瘤中建立新的肿瘤信号轴EGFR-Stat3-Smad7-TGF-b的通性。实际上，它将为开发有效治疗egfr驱动肿瘤的新方法提供指导。

Growth factor and cytokine signalling networks control many aspects of cell behaviour such as proliferation, survival, migration, invasive capabilities, transformation and differentiation. In normal cells, these complex signalling pathways are tightly regulated. Alterations of these signals are often found to cause, directly or indirectly, tumour formation. Transforming Growth Factor-b (TGF-b) and Epidermal Growth Factor (EGF) signalling pathways are both independently implicated as key regulators in tumour formation and as such they are potential therapeutic targets. However, while both pathways have been studied extensively, little is known about the cross-talk between the TGF-b and EGF pathways. This project will establish the generality of a new tumor signaling axis, namely EGFR-Stat3-Smad7-TGF-b in EGFR-overexpressing tumors. Practically, it will provide guidelines for the development of new approaches for treating effectively the EGFR-driven tumors.