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SHPCS 2013:胰腺癌的分子标志物:整合素(Integrin)α6β4

2013-08-22 Kathleen L.O'Connor MedSci原创

        第四届胰腺癌上海论坛(SHPCS)上,Kathleen L.O'Connor进行胰腺癌相关报告。侵袭和转移是导致大多数肿瘤患者治疗失败和死亡最主要原因,其过程涉及机体一系列基因结构和功能的异常,其中黏附分子起着重要的作用。整合素( integrins) 是肿瘤细胞表面的一种黏附分子,它可以介导细胞间、细胞与基质间相互作用,参与肿瘤侵袭和转移

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  第四届胰腺癌上海论坛(SHPCS)上,Kathleen L.O'Connor进行胰腺癌相关报告。侵袭和转移是导致大多数肿瘤患者治疗失败和死亡最主要原因,其过程涉及机体一系列基因结构和功能的异常,其中黏附分子起着重要的作用。整合素( integrins) 是肿瘤细胞表面的一种黏附分子,它可以介导细胞间、细胞与基质间相互作用,参与肿瘤侵袭和转移的过程。整合素α6β4 是整合素家族中的重要成员之一,其在肿瘤细胞中表达量的增高或减少会影响肿瘤细胞的生物学行为。

  整合素α6β4在PDAC早期上调并在进程中持续高表达;

  整合素α6β4协调控制了胰腺癌细胞中AREG、EREG和MMP1的表达;

  在高度α6β4表达的细胞中抑制EGFR可同时阻断HGF趋化和3D培养的入侵;

  整合素α6β4和HGF信号通路刺激AREG分泌,AREG分泌可以指向前缘;

  我们已经确定在EGFR和信号通路之间有一种小的物质可以管理肿瘤细胞入侵;

  转移来的AsPC1细胞抑制了EGFR,因此建议通路绕行EGFR存在依赖。

  肿瘤的发生和转移与整合素α6β4 的密切相关性已引起国内外学者的关注,这方面的研究成果将为探求肿瘤的发生、发展机制提供重要的新线索,是未来探 求肿瘤生长机制及制定靶点治疗手段的方向之一。深入研究整合素α6β4 通路在肿瘤的发生和转移中的作用具有重要的生物学和临床意义,相关的研究有望为肿 瘤治疗提供辅助方法和药物。

原始出处:

O'Connor KL, Chen M, Towers LN.Integrin α6β4 cooperates with LPA signaling to stimulate Rac through AKAP-Lbc-mediated RhoA activation.Am J Physiol Cell Physiol. 2012 Feb 1;302(3):C605-14. 

Chen M, Sastry SK, O'Connor KL.Src kinase pathway is involved in NFAT5-mediated S100A4 induction by hyperosmotic stress in colon cancer cells.Am J Physiol Cell Physiol. 2011 May;300(5):C1155-63.

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    2013-11-28 bbjsj_1979
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    2013-09-01 Tamikia
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