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上海生科院揭示IV型胶原蛋白促进肿瘤发展的分子机制

2015-06-01 佚名 上海生命科学研究院

IV型胶原蛋白分子机制

5月19日，国际学术期刊PLOS Genetics 在线发表了中国科学院上海生命科学研究院生物化学与细胞生物学研究所葛高翔研究组的最新研究成果Minor Type IV Collagen a5 Chain Promotes Cancer Progression through Discoidin Domain Receptor-1，揭示了IV胶原蛋白肿瘤细胞自主性与非自主性的功能与作用机制。IV型

5月19日，国际学术期刊PLOS Genetics 在线发表了中国科学院上海生命科学研究院生物化学与细胞生物学研究所葛高翔研究组的最新研究成果Minor Type IV Collagen a5 Chain Promotes Cancer Progression through Discoidin Domain Receptor-1，揭示了IV胶原蛋白肿瘤细胞自主性与非自主性的功能与作用机制。

IV型胶原蛋白是组成细胞基底膜的主要结构成分。IV型胶原蛋白包含三种高度相似的胶原蛋白前体：主要类型的a1a1a2(IV)，以及次要类型的a3a4a5(IV) 和a5a5a6(IV)。葛高翔研究组博士研究生肖倩、姜妍等通过建立基因敲除小鼠模型特异性敲除次要类型IV型胶原蛋白，并结合自发肺癌小鼠模型探讨次要类型IV型胶原蛋白在肺癌发生发展中的功能及其作用机制。研究发现，IV型胶原蛋白a5链通过肿瘤细胞自主性和非自主性的机制促进肺癌发展。一方面，上皮细胞/肿瘤细胞中的a5链促进肿瘤细胞的增殖和迁移；另一方面，血管内皮细胞中的a5链促进血管形成与肿瘤血管新生。进一步的研究发现a5的缺失导致胶原蛋白受体DDR1表达的下调及下游ERK信号的失活，而a1的缺失则不影响DDR1信号通路。从而揭示结构高度相似的IV型胶原蛋白分子通过不同的细胞表面受体与胞内信号通路发挥功能。

细胞对外界刺激的反应不仅取决于细胞本身的特性，同时也受到细胞微环境的调节。肿瘤细胞与其微环境的交互通讯在肿瘤发展及转移过程中至关重要。细胞外基质作为微环境的重要组成成分，不仅为肿瘤细胞提供结构支撑，同时作为信号分子调控肿瘤细胞及血管内皮细胞等微环境间质细胞的功能。

该项研究工作得到国家自然科学基金委的经费支持。


IV型胶原蛋白促进肿瘤血管新生

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    2016-04-13 木头人513

    #上海生科院#

    0

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    2015-09-08 yourmama

    #肿瘤发展#

    0

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    2015-06-03 12498e5fm14(暂无昵称)

    #胶原蛋白#

    0