Cortactin contributes to the tumorigenicity of colorectal cancer by promoting cell proliferation
Cortactin contributes to the tumorigenicity of colorectal cancer by promoting cell proliferation
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Cortactin 通过促进细胞增殖而导致结直肠癌的致瘤性
DOI：
10.3892/or.2016.5207
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发表时间：
2016-12-01
期刊：
影响因子：
4.2
通讯作者：
Zhao, Ren
中科院分区：
文献类型：
--
作者：
Wu, Huo;Cheng, Xi;Zhao, Ren
Corpine是一种调节Arp 2/3介导的肌动蛋白聚合的支架蛋白。我们在先前的研究中表明，corneum在人类II-III期结直肠癌（CRC）组织中高度表达。在本研究中，使用集落形成和CCK-8测定，我们发现corneumen的过表达加速了CRC细胞的增殖。流式细胞仪检测显示coronin可促进G1/S期细胞周期转换。随后，我们在Tyr 421残基处构建了coronin的磷酸化突变。集落形成和CCK-8测定表明corpyn/Tyr 421 A失去了促进细胞增殖的能力。Western blot分析表明coronin激活cyclin D1，但不激活coronin/Tyr 421 A。在裸鼠中的进一步研究显示，与注射SW 480/corneumn/WT细胞的动物相比，注射SW 480/corneumn/Tyr 421 A细胞的动物的肿瘤体积和肿瘤重量都有更大的减少。因此，本研究表明，corneumn Tyr 421残基是必需的，以促进细胞增殖，在体外和体内。
Cortactin is a scaffolding protein that regulates Arp2/3-mediated actin polymerization. We showed in a previous study that cortactin was highly expressed in human stage II-III colorectal cancer (CRC) tissues. In the present study, using colony formation and CCK-8 assays, we showed that overexpression of cortactin accelerated the proliferation of CRC cells. Flow cytometric assays revealed that cortactin promoted G1/S phase cell cycle transition. Later, we constructed the phosphorylation mutation of cortactin at the Tyr421 residue. Colony formation and CCK-8 assays showed that cortactin/Tyr421A lost its ability to promote cell proliferation. Western blot analysis indicated that cortactin activated cyclin D1, but not cortactin/Tyr421A. Further study in nude mice revealed that there was a greater decrease in both tumor volume and tumor weight in animals injected with SW480/cortactin/Tyr421A cells than in those injected with SW480/cortactin/WT cells. Thus, the present study demonstrates that the cortactin Tyr421 residue is required to promote cell proliferation both in vitro and in vivo.