肿瘤抑制基因或可抑制肿瘤周围细胞群体的生长

  发表于国际杂志PLoS Biology上的一篇研究论文中，来自巴塞罗那生物医学研究院（IRB Barcelona）的研究人员通过研究揭开了肿瘤抑制基因在限制周围细胞群体生长中所扮演的重要角色，这对于理解肿瘤发生的早期事件及肿瘤起始细胞的选择提供了新的线索。
  有机体的健康发育往往依赖于组织和器官的合适生长，即在合适的时候停止生长，并且维持组织形式和功能的稳定性，而正确的发育依赖于组织细胞中营养的可用性，而细胞中营养是否可以受到了细胞内和细胞间多种信号机制的控制，而信号的打断会引发组织或器官的不平衡生长，从而引发癌症的发生。
  名为TOR和PI3K的两种信号通路可以通过营养的有效性来调节组织的生长，而且这两种通路在人类癌症中处于频繁激活的状态，本文研究中研究者发现，TOR和PI3K信号通路的国度激活不仅会引发细胞和组织的过度生长，而且会抑制周围细胞群体的生长。研究者发现了一种名为Dally的蛋白聚糖，其可以调节人类机体中TGF-β或Dpp促生长信号分子的扩散、稳定性和活性，而该分子也受到上述两种通路的调节，并且接到了周围群体细胞生长的效应。
  研究者Ana Ferreira说道，PTEN作为负向调节PI3K通路的基因，其在人类癌症的肿瘤抑制子中常常处于缺失的状态，而理解该通路是否会影响哺乳动物机体TGF-β的扩散或可帮助我们深入理解肿瘤的发生以及对肿瘤起始细胞的选择。肿瘤起始细胞可以根据其竞争限制生长因子的能力来进行选择，而且这种能力或可限制肿瘤细胞周围细胞群体的生长；据估计，有7%的前列腺癌患者在诊断时都处于缺失PTEN基因的状态，因此后期研究癌症的发病机理对于开发新型靶向疗法或将带来巨大帮助。（转化医学网360zhyx.com）
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转化医学网推荐的原文摘要：

Dally Proteoglycan Mediates the Autonomous and Nonautonomous Effects on Tissue Growth Caused by Activation of the PI3K and TOR Pathways
PLoS Biology   DOI: 10.1371/journal.pbio.1002239
Ana Ferreira, Marco Milán 
How cells acquiring mutations in tumor suppressor genes outcompete neighboring wild-type cells is poorly understood. The phosphatidylinositol 3-kinase (PI3K)–phosphatase with tensin homology (PTEN) and tuberous sclerosis complex (TSC)-target of rapamycin (TOR) pathways are frequently activated in human cancer, and this activation is often causative of tumorigenesis. We utilized the Gal4-UAS system in Drosophila imaginal primordia, highly proliferative and growing tissues, to analyze the impact of restricted activation of these pathways on neighboring wild-type cell populations. Activation of these pathways leads to an autonomous induction of tissue overgrowth and to a remarkable nonautonomous reduction in growth and proliferation rates of adjacent cell populations. This nonautonomous response occurs independently of where these pathways are activated, is functional all throughout development, takes place across compartments, and is distinct from cell competition. The observed autonomous and nonautonomous effects on tissue growth rely on the up-regulation of the proteoglycan Dally, a major element involved in modulating the spreading, stability, and activity of the growth promoting Decapentaplegic (Dpp)/transforming growth factor β(TGF-β) signaling molecule. Our findings indicate that a reduction in the amount of available growth factors contributes to the outcompetition of wild-type cells by overgrowing cell populations. During normal development, the PI3K/PTEN and TSC/TOR pathways play a major role in sensing nutrient availability and modulating the final size of any developing organ. We present evidence that Dally also contributes to integrating nutrient sensing and organ scaling, the fitting of pattern to size.