Novel anticancer agent, SQAP, binds to focal adhesion kinase and modulates its activity.
Novel anticancer agent, SQAP, binds to focal adhesion kinase and modulates its activity.
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DOI：
10.1038/srep15136
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发表时间：
2015-10-12
影响因子：
4.6
通讯作者：
Sugawara F
中科院分区：
文献类型：
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作者：
Izaguirre-Carbonell J;Kawakubo H;Murata H;Tanabe A;Takeuchi T;Kusayanagi T;Tsukuda S;Hirakawa T;Iwabata K;Kanai Y;Ohta K;Miura M;Sakaguchi K;Matsunaga S;Sahara H;Kamisuki S;Sugawara F
SQAP是通过对天然化合物进行结构修饰而获得的一种新型且有前途的抗癌剂。SQAP抑制体内血管生成，导致缺氧增加和肿瘤体积减小。在这项研究中，SQAP改变肿瘤微环境的机制是通过T7噬菌体展示筛选的应用来揭示的。该方法鉴定了五种SQAP结合蛋白，包括固醇载体蛋白2、多功能酶2型、蛋白酶体泛素受体、UV切除修复蛋白和粘着斑激酶（FAK）。通过表面等离子体共振分析证实了所有的相互作用。由于FAK在细胞更新和血管生成中起重要作用，因此SQAP对FAK的影响是本研究的主要目标。SQAP降低人脐静脉内皮细胞和A549癌细胞FAK磷酸化和细胞迁移。这些结果表明，抑制FAK磷酸化作为SQAP的抗血管生成活性的机制。
SQAP is a novel and promising anticancer agent that was obtained by structural modifications from a natural compound. SQAP inhibits angiogenesis in vivo resulting in increased hypoxia and reduced tumor volume. In this study, the mechanism by which SQAP modifies the tumor microenvironment was revealed through the application of a T7 phage display screening. This approach identified five SQAP-binding proteins including sterol carrier protein 2, multifunctional enzyme type 2, proteasomal ubiquitin receptor, UV excision repair protein and focal adhesion kinase (FAK). All the interactions were confirmed by surface plasmon resonance analysis. Since FAK plays an important role in cell turnover and angiogenesis, the influence of SQAP on FAK was the principal goal of this study. SQAP decreased FAK phosphorylation and cell migration in human umbilical vein endothelial cells and A549 cancer cells. These findings suggest that inhibition of FAK phosphorylation works as the mechanism for the anti-angiogenesis activity of SQAP.