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

EGFR 驱动的肿瘤发展过程中 TGF-β 细胞抑制调节的丧失

• 批准号: nhmrc : 433618
• 负责人: Dr Hong-Jian Zhu
• 金额: $ 40.34万
• 依托单位: The University of Melbourne
• 依托单位国家: 澳大利亚
• 项目类别: Project Grants
• 财政年份: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/loss-cytostatic-regulation-tumor-development/98816
• 关键词: Loss; cytostatic; regulation; TGF; beta

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.

生长因子和细胞因子信号网络控制细胞行为的许多方面，例如增殖、存活、迁移、侵入能力、转化和分化。在正常细胞中，这些复杂的信号通路受到严格的调节。这些信号的改变经常被发现直接或间接地导致肿瘤形成。转化生长因子-b（TGF-b）和表皮生长因子（EGF）信号传导途径都独立地涉及作为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，虽然这两种途径都被广泛研究，但对TGF-β和EGF途径之间的相互作用知之甚少。该项目将建立一个新的肿瘤信号传导轴，即EGFR-Stat 3-Smad 7-TGF-b在EGFR过表达肿瘤中的普遍性。实际上，它将为开发有效治疗EGFR驱动的肿瘤的新方法提供指导。