2012年8月28日 讯 /生物谷BIOON/ --美国科学家已经发出的称为钉肽的一种人造分子，可以关闭促癌Wnt信号分子来抑制癌症。据哈佛医学院的研究人员称，钉肽迄今只在小鼠中进行测试。
Wnt信号分子网络控制一系列正常细胞的生物学过程。但该网络的调节失控可能会导致癌症的发生。Wnt信号通路中故障被证实在多种癌症特别是肠癌中存在。新的肽模拟一种天然分子BCL9的结构，BCL9对Wnt信号在肿瘤细胞中的传输是必要的，但BCL9在健康细胞却是不存在的。由于其相似BCL9，该合成肽能阻断正在发送的信号，切断癌细胞内的驱动信号。
剑桥分子生物学实验室、英国癌症研究中心的科学家Mariann Bienz博士说，科学家们一直试图找到方法来阻止Wnt信号或与之有相互作用的分子来抑制肿瘤。她说：癌症研究的最大挑战之一是找到方法抑制促进癌症疾病发生发展的分子，阻止细胞内蛋白质之间的相互作用是非常困难的。在这项研究工作种，我们证实阻断促癌蛋白BCL9和β-catenin之间的相互作用是可能的，而这两个关键蛋白在Wnt信号转导通路中至关重要。
她还表示，重大的挑战依然存在。科学家还不知道是否以钉肽为基础的治疗可以有效地在细胞内实现他们的治疗目的，同时更不知道钉肽对癌症患者临床试验是否有效。该研究成果发表在Science Translational Medicine杂志上。（生物谷：Bioon.com）
doi:10.1126/scitranslmed.3003808
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Targeted Disruption of the BCL9/β-Catenin Complex Inhibits Oncogenic Wnt Signaling
Takada, K. et al.
Deregulated Wnt/β-catenin signaling underlies the pathogenesis of a broad range of human cancers, yet the development of targeted therapies to disrupt the resulting aberrant transcription has proved difficult because the pathway comprises large protein interaction surfaces and regulates many homeostatic functions. Therefore, we have directed our efforts toward blocking the interaction of β-catenin with B cell lymphoma 9 (BCL9), a co-activator for β-catenin–mediated transcription that is highly expressed in tumors but not in the cells of origin. BCL9 drives β-catenin signaling through direct binding mediated by its α-helical homology domain 2. We developed a stabilized α helix of BCL9 (SAH-BCL9), which we show targets β-catenin, dissociates native β-catenin/BCL9 complexes, selectively suppresses Wnt transcription, and exhibits mechanism-based antitumor effects. SAH-BCL9 also suppresses tumor growth, angiogenesis, invasion, and metastasis in mouse xenograft models of Colo320 colorectal carcinoma and INA-6 multiple myeloma. By inhibiting the BCL9–β-catenin interaction and selectively suppressing oncogenic Wnt transcription, SAH-BCL9 may serve as a prototype therapeutic agent for cancers driven by deregulated Wnt signaling.
