Cell Rep:HER2+乳腺癌治疗新希望!增殖蔓延多步骤共同靶点被发现

2018-05-03 Michael 转化医学网

转移是一个复杂的多步骤过程,涉及瘤内细胞侵入随后进入循环(血管内浸润),癌细胞侵入(外渗)并在远处组织中存活并生长为转移病灶。不幸的是,一旦疾病扩散到次要器官,它便变得无法治愈。在乳腺癌中,三阴性(TNBC)和HER2阳性(HER2 +)亚型由于其转移倾向而与生存率低密切相关。

转移是一个复杂的多步骤过程,涉及瘤内细胞侵入随后进入循环(血管内浸润),癌细胞侵入(外渗)并在远处组织中存活并生长为转移病灶。不幸的是,一旦疾病扩散到次要器官,它便变得无法治愈。在乳腺癌中,三阴性(TNBC)和HER2阳性(HER2 +)亚型由于其转移倾向而与生存率低密切相关。

HER2是受体酪氨酸激酶(RTKs)表皮生长因子受体(EGFR)的成员,其在≥20%的人乳腺癌中过表达或扩增并且介导传递与肿瘤生长,侵袭和转移相关的信号。尽管一些罹患HER2 +乳腺癌的患者受益于抗HER2治疗,但一部分患者可能无反应或会产生抗药性并随后出现转移性疾病的复发。因此,明确HER2促进癌症扩散的分子机制可为新的抗转移治疗提供新的策略。


该实验设计原理图

AXL,TYRO3和MER共同构成RTK的TAM家族。在这个家族内,AXL被其配体GAS6特异性激活。尽管TAM对于胚胎发育是不必要的,但它们在抑制先天免疫方面有着重要的作用。 AXL广泛表达于实体癌症中,包括乳腺癌,非小细胞肺癌卵巢癌和透明细胞肾癌,其水平与增加的转移风险相关。在乳腺癌细胞系中,AXL表达限于具有三重阴性基因标签的细胞,使得AXL被视为该乳腺癌亚型的标志物。



HER2与AXL相互作用,增强HER2的稳定性及促进其表达

通过一系列遗传和功能检测,研究人员证明了AXL在HER2 +乳腺癌中有促进转移的作用。通过使用遗传方法,研究人员发现GAS6对于体内HER2驱动的转移并非完全必要。相反,AXL似乎与HER2发生相互作用,从而绕过GAS6激活途径,这导致AXL驱动HER2+乳腺癌转移的发生。



AXL能够促进HER2+乳腺肿瘤细胞转移

EMT的可塑性对于有效转移至关重要。获得EMT特征可促进原发性肿瘤的迁移、血管内渗透和促进循环中的细胞进行外渗。研究人员发现AXL对促进HER2 +癌细胞的渗透作用是必不可少的,同时他们也发现AXL是TGF-b诱导的HER2 +癌细胞外渗的关键介导因子。

因此,可能需要AXL以允许细胞用于外渗的有效TGF-b重编程。这些数据证明AXL有强烈地促肿瘤转移的作用。同时,该实验的数据表明抗AXL治疗可降低HER2 +肿瘤的转移水平。这对未来治疗HER2 +肿瘤具有里程碑意义。

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    2018-08-28 维他命
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    2018-05-04 珙桐
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    2018-05-04 张新亮1853311252142e2fm

    好文献学习了

    0

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    2018-05-03 有备才能无患

    转移是一个复杂的多步骤过程.涉及瘤内细胞侵入随后进入循环(血管内浸润).癌细胞侵入(外渗)并在远处组织中存活并生长为转移病灶.不幸的是.一旦疾病扩散到次要器官.它便变得无法治愈.在乳腺癌中.三阴性(TNBC)和HER2阳性(HER2+)亚型由于其转移倾向而与生存率低密切相关.

    0

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    2018-05-03 329523732

    不错

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=1960879, encodeId=c88319608e99b, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, 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=Tue Aug 28 03:18:00 CST 2018, time=2018-08-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1969977, encodeId=f46e19699e74c, content=<a href='/topic/show?id=ec345834075' target=_blank style='color:#2F92EE;'>#新希望#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58340, encryptionId=ec345834075, topicName=新希望)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=25d7319, createdName=珙桐, createdTime=Fri May 04 12:18:00 CST 2018, time=2018-05-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1870610, encodeId=5db318e0610d6, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Mon Feb 11 09:18:00 CST 2019, time=2019-02-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=311830, encodeId=c498311830e3, content=好文献学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b5a62240667, createdName=张新亮1853311252142e2fm, createdTime=Fri May 04 07:21:47 CST 2018, time=2018-05-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=311723, encodeId=a74a311e23bd, content=转移是一个复杂的多步骤过程.涉及瘤内细胞侵入随后进入循环(血管内浸润).癌细胞侵入(外渗)并在远处组织中存活并生长为转移病灶.不幸的是.一旦疾病扩散到次要器官.它便变得无法治愈.在乳腺癌中.三阴性(TNBC)和HER2阳性(HER2+)亚型由于其转移倾向而与生存率低密切相关., beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7cJ6ejWUr2nIia8qOvAKNdLHr32Df6G8iaoaOx6pHaoiacwp26DaslxZHCGbibZhhCGven4rvmWP60GahtzgFjgCjR/0, createdBy=6b111703011, createdName=有备才能无患, createdTime=Thu May 03 22:28:14 CST 2018, time=2018-05-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=311692, encodeId=611931169210, content=不错, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/2EVCwc9WmQS6ec99H2TX8ejmR40xYjwrIcrqjAnibV36aicL1sLxc21rhpZnqTOxk33HP44iayEwo6qYXqgZvdRtA/132, createdBy=d0d01573846, createdName=329523732, createdTime=Thu May 03 20:02:09 CST 2018, time=2018-05-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=311681, encodeId=7bce311681f1, content=学习了.涨知识了!, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3zMoyicyo6ia9f4IuLQAwZoxD6Hx4ibd5CMcOCYhStY6oDibbKK6O2X8iaicldO5ib8j1iapOIobIKCGiczU2A/0, createdBy=56251941490, createdName=虈亣靌, createdTime=Thu May 03 19:32:57 CST 2018, time=2018-05-03, status=1, ipAttribution=)]
    2018-05-03 虈亣靌

    学习了.涨知识了!

    0

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