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Cell:揭示癌基因调节肿瘤细胞信号转导的分子机制

2016-04-18 佚名 不详

图片摘自:thesundaytimes.co.uk

2016年4月18日 讯 /生物谷BIOON/ --近日,来自赫特福德大学的研究人员通过研究揭示了关键性致癌基因调节肿瘤细胞信号的特殊机制,相关研究刊登于国际杂志Cell上。

实体癌症是一种包含肿瘤细胞和基质细胞的异型细胞系统,肿瘤细胞癌基因对基质细胞的抑制会明显影响癌症生物学的机制,而且异常的肿瘤基质信号会调节许多癌症的标志;当单一的肿瘤机制信号的癌基因驱动调节子被鉴别时,目前研究人员并不清楚通过整个异型细胞系统的癌基因依赖性信号的传播机制,因此本文研究中研究人员以癌基因信号为视角揭示了癌基因调节离体状态肿瘤细胞的分子机制。

研究者Christopher J. Tape指出,癌基因突变会调节肿瘤细胞和附近基质细胞的信号,文章中我们发现了癌基因KRAS会通过基质细胞来调节肿瘤细胞的信号,通过将细胞特异性的蛋白质组标记技术同多元化的磷酸化蛋白质组学(PhosphoProteomics)技术进行研究,我们就分析了胰腺导管腺癌细胞中异型细胞KRAS的信号通路。

肿瘤细胞中的KRAS往往会参与异型纤维母细胞的信号转导,随后就会诱导肿瘤细胞中相互转化的信号通路的发生,而这种相互信号的发生往往会利用额外的激酶并且使得细胞自主的KRAS调节性的信号节点数量加倍;因此互换的癌基因KRAS通常会在肿瘤细胞诱导产生磷酸化蛋白质组和总的蛋白质组,而这些和细胞自主的癌基因KRAS并不相同;研究者还发现,互换的信号可以调节肿瘤细胞的增殖以及细胞凋亡,同时还会以IGF1R/AXLAKT为中心来增加线粒体的容量。

最后研究者Claus Jorgensen说道,本文研究结果表明,癌基因的信号通路或许可以被认为是一种异型细胞的信号传输过程,而且癌基因KRAS可以通过一种基质细胞的互换信号来调节肿瘤细胞的信号转导,这对于后期揭示癌症发病的机制及开发新型个体化疗法或将提供新的线索和思路。(生物谷Bioon.com)

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Oncogenic KRAS Regulates Tumor Cell Signaling via Stromal Reciprocation

Christopher J. Tape, Stephanie Ling, Maria Dimitriadi4, Kelly M. McMahon, Jonathan D. Worboys, Hui Sun Leong, Ida C. Norrie, Crispin J. Miller, George Poulogiannis, Douglas A. Lauffenburger, Claus Jørgensen

Oncogenic mutations regulate signaling within both tumor cells and adjacent stromal cells. Here, we show that oncogenic KRAS (KRASG12D) also regulates tumor cell signaling via stromal cells. By combining cell-specific proteome labeling with multivariate phosphoproteomics, we analyzed heterocellular KRASG12D signaling in pancreatic ductal adenocarcinoma (PDA) cells. Tumor cell KRASG12D engages heterotypic fibroblasts, which subsequently instigate reciprocal signaling in the tumor cells. Reciprocal signaling employs additional kinases and doubles the number of regulated signaling nodes from cell-autonomous KRASG12D. Consequently, reciprocal KRASG12D produces a tumor cell phosphoproteome and total proteome that is distinct from cell-autonomous KRASG12D alone. Reciprocal signaling regulates tumor cell proliferation and apoptosis and increases mitochondrial capacity via an IGF1R/AXL-AKT axis. These results demonstrate that oncogene signaling should be viewed as a heterocellular process and that our existing cell-autonomous perspective underrepresents the extent of oncogene signaling in cancer.

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    2016-06-02 维他命
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  5. [GetPortalCommentsPageByObjectIdResponse(id=1804943, encodeId=b47c1804943ed, content=<a href='/topic/show?id=4a14e778636' target=_blank style='color:#2F92EE;'>#细胞信号转导#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77786, encryptionId=4a14e778636, topicName=细胞信号转导)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c737344, createdName=lg.zhao, createdTime=Mon Nov 07 11:27:00 CST 2016, time=2016-11-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1959598, encodeId=d0c519595984e, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Thu Jun 02 18:27:00 CST 2016, time=2016-06-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1869341, encodeId=fb031869341b7, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Tue Dec 20 09:27:00 CST 2016, time=2016-12-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1312929, encodeId=cd7613129297f, content=<a href='/topic/show?id=4ce783062c7' target=_blank style='color:#2F92EE;'>#肿瘤细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83062, encryptionId=4ce783062c7, topicName=肿瘤细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c859411, createdName=hmwwww, createdTime=Wed Apr 20 00:27:00 CST 2016, time=2016-04-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1373885, encodeId=3d5513e3885e2, content=<a href='/topic/show?id=3644e1286f1' target=_blank style='color:#2F92EE;'>#癌基因#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=71286, encryptionId=3644e1286f1, topicName=癌基因)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ee7b365, createdName=zhucaizhong7766, createdTime=Wed Apr 20 00:27:00 CST 2016, time=2016-04-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=79456, encodeId=45a6e94563f, content=高大上的文章, beContent=null, objectType=article, channel=null, level=null, likeNumber=171, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=240a1683959, createdName=李继凯, createdTime=Tue Apr 19 01:03:00 CST 2016, time=2016-04-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=79457, encodeId=1f82e9457dd, content=值得关注, beContent=null, objectType=article, channel=null, level=null, likeNumber=221, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=240a1683959, createdName=李继凯, createdTime=Tue Apr 19 01:03:00 CST 2016, time=2016-04-19, status=1, ipAttribution=)]
  6. [GetPortalCommentsPageByObjectIdResponse(id=1804943, encodeId=b47c1804943ed, content=<a href='/topic/show?id=4a14e778636' target=_blank style='color:#2F92EE;'>#细胞信号转导#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77786, encryptionId=4a14e778636, topicName=细胞信号转导)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c737344, createdName=lg.zhao, createdTime=Mon Nov 07 11:27:00 CST 2016, time=2016-11-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1959598, encodeId=d0c519595984e, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Thu Jun 02 18:27:00 CST 2016, time=2016-06-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1869341, encodeId=fb031869341b7, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Tue Dec 20 09:27:00 CST 2016, time=2016-12-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1312929, encodeId=cd7613129297f, content=<a href='/topic/show?id=4ce783062c7' target=_blank style='color:#2F92EE;'>#肿瘤细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83062, encryptionId=4ce783062c7, topicName=肿瘤细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c859411, createdName=hmwwww, createdTime=Wed Apr 20 00:27:00 CST 2016, time=2016-04-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1373885, encodeId=3d5513e3885e2, content=<a href='/topic/show?id=3644e1286f1' target=_blank style='color:#2F92EE;'>#癌基因#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=71286, encryptionId=3644e1286f1, topicName=癌基因)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ee7b365, createdName=zhucaizhong7766, createdTime=Wed Apr 20 00:27:00 CST 2016, time=2016-04-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=79456, encodeId=45a6e94563f, content=高大上的文章, beContent=null, objectType=article, channel=null, level=null, likeNumber=171, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=240a1683959, createdName=李继凯, createdTime=Tue Apr 19 01:03:00 CST 2016, time=2016-04-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=79457, encodeId=1f82e9457dd, content=值得关注, beContent=null, objectType=article, channel=null, level=null, likeNumber=221, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=240a1683959, createdName=李继凯, createdTime=Tue Apr 19 01:03:00 CST 2016, time=2016-04-19, status=1, ipAttribution=)]
    2016-04-19 李继凯

    高大上的文章

    0

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    2016-04-19 李继凯

    值得关注

    0

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