2012年8月28日 訊 /生物谷BIOON/ --美國(guó)科學(xué)家已經(jīng)發(fā)出的稱為釘肽的一種人造分子,，可以關(guān)閉促癌Wnt信號(hào)分子來(lái)抑制癌癥,。據(jù)哈佛醫(yī)學(xué)院的研究人員稱，釘肽迄今只在小鼠中進(jìn)行測(cè)試,。
Wnt信號(hào)分子網(wǎng)絡(luò)控制一系列正常細(xì)胞的生物學(xué)過(guò)程,。但該網(wǎng)絡(luò)的調(diào)節(jié)失控可能會(huì)導(dǎo)致癌癥的發(fā)生,。Wnt信號(hào)通路中故障被證實(shí)在多種癌癥特別是腸癌中存在。新的肽模擬一種天然分子BCL9的結(jié)構(gòu),，BCL9對(duì)Wnt信號(hào)在腫瘤細(xì)胞中的傳輸是必要的,，但BCL9在健康細(xì)胞卻是不存在的。由于其相似BCL9,，該合成肽能阻斷正在發(fā)送的信號(hào),，切斷癌細(xì)胞內(nèi)的驅(qū)動(dòng)信號(hào)。
劍橋分子生物學(xué)實(shí)驗(yàn)室,、英國(guó)癌癥研究中心的科學(xué)家Mariann Bienz博士說(shuō),，科學(xué)家們一直試圖找到方法來(lái)阻止Wnt信號(hào)或與之有相互作用的分子來(lái)抑制腫瘤。她說(shuō)：癌癥研究的最大挑戰(zhàn)之一是找到方法抑制促進(jìn)癌癥疾病發(fā)生發(fā)展的分子,，阻止細(xì)胞內(nèi)蛋白質(zhì)之間的相互作用是非常困難的,。在這項(xiàng)研究工作種，我們證實(shí)阻斷促癌蛋白BCL9和β-catenin之間的相互作用是可能的,，而這兩個(gè)關(guān)鍵蛋白在Wnt信號(hào)轉(zhuǎn)導(dǎo)通路中至關(guān)重要,。
她還表示，重大的挑戰(zhàn)依然存在,?？茖W(xué)家還不知道是否以釘肽為基礎(chǔ)的治療可以有效地在細(xì)胞內(nèi)實(shí)現(xiàn)他們的治療目的，同時(shí)更不知道釘肽對(duì)癌癥患者臨床試驗(yàn)是否有效,。該研究成果發(fā)表在Science Translational Medicine雜志上,。（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.
