l14107cb 发表于 2024-10-3 18:11:18

Science Advances | 厦门大学发掘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;"><img src="https://mmbiz.qpic.cn/mmbiz_gif/Nd3V8nVKhZXiacyv4ICibrE7c7OnkhMh0dkicwdiadTlAqh7G4v92sUP5EgMo2NDf2SEW0pfKtoADV4Hh9cwceiaREg/640?wx_fmt=gif&amp;tp=webp&amp;wxfrom=5&amp;wx_lazy=1" style="width: 50%; margin-bottom: 20px;"></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;">( EMT)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>。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,TGFβ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>,一项<span style="color: black;">发布</span>在<strong style="color: blue;">《Science Advances》(IF=12.804)</strong>上的来自<strong style="color: blue;">厦门大学<span style="color: black;">王</span><span style="color: black;">洪睿、付国、</span><span style="color: black;">陈晓蕾团队</span></strong>的<span style="color: black;">科研</span>成果<strong style="color: blue;">为<span style="color: black;">EMT的细胞连接解离<span style="color: black;">供给</span>了新的机制解析。</span></strong></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&amp;tp=webp&amp;wxfrom=5&amp;wx_lazy=1&amp;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<strong style="color: blue;">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。</strong></span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">在上游信号TGFβ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>TGFβ<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><span style="color: black;">参考文献:</span><span style="color: black;">&nbsp;</span><span style="color: black;">Qingang&nbsp;Wu</span><span style="color: black;">et al.&nbsp;Monoubiquitination of p120-catenin is essential for TGFβ-induced epithelial-mesenchymal transition and tumor metastasis.&nbsp;Science Advances. (2020)</span>
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