王洪睿/付国/陈晓蕾团队供给EMT细胞间解离新机制
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;"><strong style="color: blue;"><span style="color: black;">责编 | 酶美</span></strong></span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;"><span style="color: black;">上皮间质细胞转化</span></strong><span style="color: black;">（epithelial-mesenchymal transition, EMT）</span><span style="color: black;"><span style="color: black;">指的是</span>上皮细胞向间充质细胞转化的过程，不仅在胚胎<span style="color: black;">生长</span>等生理过程中起着重要<span style="color: black;">功效</span>，<span style="color: black;">亦</span>与上皮细胞<span style="color: black;">源自</span>的肿瘤的扩散转移密切<span style="color: black;">关联</span>。上皮细胞彼此之间<span style="color: black;">经过</span><span style="color: black;">包含</span>紧密连接</span><span style="color: black;">（tight junction, TJ）</span><span style="color: black;">和黏附连接</span><span style="color: black;">（adherens junction, AJ）</span><span style="color: black;">在内的细胞连接方式形成<span style="color: black;">拥有</span>顶端-基底端极性</span><span style="color: black;">（apical-basal polarity）</span><span style="color: black;">的规则<span style="color: black;">摆列</span>的上皮组织。在EMT过程中，上皮细胞会表现出细胞连接解离、极性丧失、迁移能力<span style="color: black;">加强</span>等特征。虽然细胞连接的解离被认为是EMT的标志性事件，然而人们对在EMT过程中<span style="color: black;">导致</span>细胞连接解离的分子机制却还是很不清楚。</span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">2005年加拿大多伦多大学Jeffrey Wrana实验室的<span style="color: black;">科研</span>工作<span style="color: black;">显示</span>，在TG</span><span style="color: black;">Fβ诱</span><span style="color: black;">导的EMT过程中，TGF<span style="color: black;">β</span>受体会<span style="color: black;">经过</span>磷酸化细胞极性<span style="color: black;">关联</span>分子Par6来招募E3泛素连接酶Smurf1到上皮细胞的紧密连接处，泛素化降解在细胞骨架<span style="color: black;">创立</span>和维持中起重要<span style="color: black;">功效</span>的小G蛋白RhoA，<span style="color: black;">因此呢</span>认为在EMT过程中是<span style="color: black;">经过</span>Smurf1降解RhoA<span style="color: black;">引起</span>细胞骨架的改变使得细胞连接解离。</span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;"><span style="color: black;">近期</span>，<strong style="color: blue;">Science Advances</strong><span style="color: black;">发布</span>了厦门大学王洪睿、付国、陈晓蕾团队的成果，题为：</span><span style="color: black;"><strong style="color: blue;">Monoubiquitination of p120-catenin is essential for TGF</strong></span><span style="color: black;"><strong style="color: blue;">β</strong></span><span style="color: black;"><strong style="color: blue;">-induced epithelial-mesenchymal transition and tumor metastasis</strong></span><span style="color: black;">。<span style="color: black;">她们</span>的成果为EMT的细胞连接解离<span style="color: black;">供给</span>了新的机制解析。</span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><img src="https://mmbiz.qpic.cn/mmbiz_png/PlqGiacEDZrklJLAaIUTnb9nDtet0FYoVwianWlHHiczKT6yKo8GQzXQH8pQx8ibAQtfR24FteOiaibJbthFFApqyKbg/640?wx_fmt=png&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;"></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;"><span style="color: black;">科研</span><span style="color: black;">发掘</span>在EMT过程中细胞连接的解离不是简单的细胞骨架改变<span style="color: black;">引起</span>的“坍塌”，而是一个更为精细调控的先是黏附连接的解离，再是细胞骨架的改变和紧密连接解离的多<span style="color: black;">过程</span>的过程。在上游信号TGF<span style="color: black;">β</span>的刺激下，细胞要招募Smurf1到细胞连接区域，<span style="color: black;">同期</span>要促进ERK激酶对黏附连接复合体中的一个核心分子p120-catenin的T900进行磷酸化修饰，<span style="color: black;">从而</span>促进p120-catenin与Smurf1的结合，使得Smurf1对p120-catenin进行单泛素化修饰。单泛素化修饰的p120-catenin会从黏附链接复合体中解离出来，从而<span style="color: black;">引起</span>黏附连接的解离。阻断p120-catenin的泛素化修饰或T900磷酸化修饰或不仅<span style="color: black;">能够</span><span style="color: black;">明显</span>地<span style="color: black;">控制</span>TGF<span style="color: black;">β</span><span style="color: black;">导致</span>的黏附连接的解离，<span style="color: black;">亦</span>会<span style="color: black;">控制</span>RhoA的降解和细胞骨架的改变以及紧密连接的解离。</span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">最新的这项<span style="color: black;">科研</span><span style="color: black;">发掘</span>，</span><span style="color: black;"><strong style="color: blue;">在人的乳腺癌样品中p120-catenin的T900磷酸化修饰程度与肿瘤的侵袭转移密切<span style="color: black;">关联</span>，并且阻断p120-catenin的T900磷酸化修饰或泛素化修饰<span style="color: black;">能够</span>很大程度地防止肿瘤细胞在小鼠<span style="color: black;">身体</span>的扩散转移，为检测和防止癌症的扩散转移<span style="color: black;">供给</span>了新的靶点和思路。</strong></span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">厦门大学生命科学学院<strong style="color: blue;">吴勤刚</strong>、</span><span style="color: black;"><strong style="color: blue;">李高</strong></span><span style="color: black;">、<strong style="color: blue;">文成文</strong>、</span><span style="color: black;"><strong style="color: blue;">曾涛玲</strong></span><span style="color: black;">为<span style="color: black;">一起</span><span style="color: black;">第1</span>作者，</span><span style="color: black;"><strong style="color: blue;">王洪睿</strong></span><span style="color: black;">、</span><span style="color: black;"><strong style="color: blue;">付国</strong></span><span style="color: black;">、</span><span style="color: black;"><strong style="color: blue;">陈晓蕾</strong></span><span style="color: black;">为<span style="color: black;">一起</span>通讯作者。</span></p><strong style="color: blue;"><span style="color: black;">原文链接：</span></strong><strong style="color: blue;"><span style="color: black;">https://advances.sciencemag.org/content/advances/6/4/eaay9819.full.pdf</span></strong><span style="color: black;">制版人：珂</span><img src="https://mmbiz.qpic.cn/mmbiz_jpg/PlqGiacEDZrlaBZicVnjmMHeOaWibGqt5icX2nVwIPLHuIr89VFPWKhU4wX70jkYicdy9vYsZY7sYbVhmWQDxM2HAbA/640?wx_fmt=jpeg&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;">
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