Oncogene:YB1/EphA2信号增强能够促进肾细胞癌获得性舒尼替尼耐药和转移潜能

2020-09-05 AlexYang MedSci原创

VHL变异是肾透明细胞癌(ccRCC)中最常见的致瘤性病变,可导致HIF/VEGF通路的持续激活和不受控制的癌症进展。诸如舒尼替尼等受体酪氨酸激酶(RTK)抑制剂已被证明在转移性肾细胞癌(mRCC)中

VHL变异是肾透明细胞癌(ccRCC)中最常见的致瘤性病变,可导致HIF/VEGF通路的持续激活和不受控制的癌症进展。诸如舒尼替尼等受体酪氨酸激酶(RTK)抑制剂已被证明在转移性肾细胞癌(mRCC)中能靶向致瘤信号通路,延缓肿瘤进展,改善患者预后。虽然前人已经报道了舒尼替尼耐药的多种机制,但克服这种耐药的方法尚不清楚。

在近期发表在Oncogene杂志的一项研究中,来自华中科技大学的研究人员发现,Y-box结合蛋白1 (YB1,一种多重耐药性相关蛋白)和EphA2(红细胞生成素产生的肝细胞(Eph)受体家族成员,属于RTK家族)表达的增加介导了舒尼替耐药性,并且mRCC对YB1和 EphA2表现出了大量表型依赖。此外,他们的研究证实YB1通过调控EphA2信号通路来促进ccRCC的侵袭、转移和对舒尼替尼的耐药性。通过小分子抑制剂ALW-II-41-27对EphA2进行药理抑制,可降低耐舒尼替尼肿瘤细胞的增殖,在体内抑制肿瘤生长,恢复耐舒尼替尼肿瘤细胞在体内外对舒尼替尼的敏感性。YB1从机制上通过抑制蛋白酶体降解途径,维持EphA2蛋白的稳定性,从而提高EphA2蛋白水平。

YB1通过介导EphA2信号诱导舒尼替尼抗性

最后,研究人员指出,他们的发现为前瞻性的、有目的性的靶向ccRCC转移和RTK定向治疗耐药性提供了理论上的解释。

原始出处:

Hailong Ruan, Sen Li, Lin Bao et al. Enhanced YB1/EphA2 axis signaling promotes acquired resistance to sunitinib and metastatic potential in renal cell carcinoma. Oncogene. August 2020

 

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    2020-11-05 cy0324
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    2020-09-10 1474c43fm46暂无昵称

    不错

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=2049329, encodeId=72f82049329bc, content=<a href='/topic/show?id=4363e929ad' target=_blank style='color:#2F92EE;'>#Gene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7929, encryptionId=4363e929ad, topicName=Gene)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=63a4277, createdName=cy0324, createdTime=Thu Nov 05 00:27:43 CST 2020, time=2020-11-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2042672, encodeId=d64c20426e2c0, content=<a href='/topic/show?id=999c88014ea' target=_blank style='color:#2F92EE;'>#获得性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88014, encryptionId=999c88014ea, topicName=获得性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d4b7363, createdName=pandamao2010, createdTime=Thu Dec 24 20:27:43 CST 2020, time=2020-12-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1979017, encodeId=bab619e90176f, content=<a href='/topic/show?id=3b90e79787f' target=_blank style='color:#2F92EE;'>#细胞癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77978, encryptionId=3b90e79787f, topicName=细胞癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e457184, createdName=qingting, createdTime=Sun Sep 27 09:27:43 CST 2020, time=2020-09-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=884277, encodeId=07378842e716, content=不错, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e6785205858, createdName=1474c43fm46暂无昵称, createdTime=Thu Sep 10 18:06:43 CST 2020, time=2020-09-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1558200, encodeId=2ee31558200ce, content=<a href='/topic/show?id=2f1c13349e7' target=_blank style='color:#2F92EE;'>#Oncogene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13349, encryptionId=2f1c13349e7, topicName=Oncogene)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=154614942533, createdName=zsyan, createdTime=Mon Sep 07 01:27:43 CST 2020, time=2020-09-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=883077, encodeId=9d158830e774, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200820/a50c79dfbf8443c28d9507e5ed481752/4f3848e242344bd8a14c3db699d30a7b.jpg, createdBy=da5f5248805, createdName=Mr.d, createdTime=Sun Sep 06 11:39:07 CST 2020, time=2020-09-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=882899, encodeId=6db188289958, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=101, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/g?b=oidb&k=DN2yAtxINoWbrXpDEHQs1g&s=100&t=1551532692, createdBy=8a085316034, createdName=小雪123, createdTime=Sat Sep 05 11:05:54 CST 2020, time=2020-09-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=882895, encodeId=f81d88289532, content=学习了!, beContent=null, objectType=article, channel=null, level=null, likeNumber=118, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8f435296195, createdName=ms3000000449926787, createdTime=Sat Sep 05 10:45:49 CST 2020, time=2020-09-05, status=1, ipAttribution=)]
    2020-09-07 zsyan
  6. [GetPortalCommentsPageByObjectIdResponse(id=2049329, encodeId=72f82049329bc, content=<a href='/topic/show?id=4363e929ad' target=_blank style='color:#2F92EE;'>#Gene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7929, encryptionId=4363e929ad, topicName=Gene)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=63a4277, createdName=cy0324, createdTime=Thu Nov 05 00:27:43 CST 2020, time=2020-11-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2042672, encodeId=d64c20426e2c0, content=<a href='/topic/show?id=999c88014ea' target=_blank style='color:#2F92EE;'>#获得性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88014, encryptionId=999c88014ea, topicName=获得性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d4b7363, createdName=pandamao2010, createdTime=Thu Dec 24 20:27:43 CST 2020, time=2020-12-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1979017, encodeId=bab619e90176f, content=<a href='/topic/show?id=3b90e79787f' target=_blank style='color:#2F92EE;'>#细胞癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77978, encryptionId=3b90e79787f, topicName=细胞癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e457184, createdName=qingting, createdTime=Sun Sep 27 09:27:43 CST 2020, time=2020-09-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=884277, encodeId=07378842e716, content=不错, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e6785205858, createdName=1474c43fm46暂无昵称, createdTime=Thu Sep 10 18:06:43 CST 2020, time=2020-09-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1558200, encodeId=2ee31558200ce, content=<a href='/topic/show?id=2f1c13349e7' target=_blank style='color:#2F92EE;'>#Oncogene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13349, encryptionId=2f1c13349e7, topicName=Oncogene)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=154614942533, createdName=zsyan, createdTime=Mon Sep 07 01:27:43 CST 2020, time=2020-09-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=883077, encodeId=9d158830e774, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200820/a50c79dfbf8443c28d9507e5ed481752/4f3848e242344bd8a14c3db699d30a7b.jpg, createdBy=da5f5248805, createdName=Mr.d, createdTime=Sun Sep 06 11:39:07 CST 2020, time=2020-09-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=882899, encodeId=6db188289958, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=101, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/g?b=oidb&k=DN2yAtxINoWbrXpDEHQs1g&s=100&t=1551532692, createdBy=8a085316034, createdName=小雪123, createdTime=Sat Sep 05 11:05:54 CST 2020, time=2020-09-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=882895, encodeId=f81d88289532, content=学习了!, beContent=null, objectType=article, channel=null, level=null, likeNumber=118, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8f435296195, createdName=ms3000000449926787, createdTime=Sat Sep 05 10:45:49 CST 2020, time=2020-09-05, status=1, ipAttribution=)]
    2020-09-06 Mr.d

    学习了

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=2049329, encodeId=72f82049329bc, content=<a href='/topic/show?id=4363e929ad' target=_blank style='color:#2F92EE;'>#Gene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7929, encryptionId=4363e929ad, topicName=Gene)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=63a4277, createdName=cy0324, createdTime=Thu Nov 05 00:27:43 CST 2020, time=2020-11-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2042672, encodeId=d64c20426e2c0, content=<a href='/topic/show?id=999c88014ea' target=_blank style='color:#2F92EE;'>#获得性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88014, encryptionId=999c88014ea, topicName=获得性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d4b7363, createdName=pandamao2010, createdTime=Thu Dec 24 20:27:43 CST 2020, time=2020-12-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1979017, encodeId=bab619e90176f, content=<a href='/topic/show?id=3b90e79787f' target=_blank style='color:#2F92EE;'>#细胞癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77978, encryptionId=3b90e79787f, topicName=细胞癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e457184, createdName=qingting, createdTime=Sun Sep 27 09:27:43 CST 2020, time=2020-09-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=884277, encodeId=07378842e716, content=不错, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e6785205858, createdName=1474c43fm46暂无昵称, createdTime=Thu Sep 10 18:06:43 CST 2020, time=2020-09-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1558200, encodeId=2ee31558200ce, content=<a href='/topic/show?id=2f1c13349e7' target=_blank style='color:#2F92EE;'>#Oncogene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13349, encryptionId=2f1c13349e7, topicName=Oncogene)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=154614942533, createdName=zsyan, createdTime=Mon Sep 07 01:27:43 CST 2020, time=2020-09-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=883077, encodeId=9d158830e774, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200820/a50c79dfbf8443c28d9507e5ed481752/4f3848e242344bd8a14c3db699d30a7b.jpg, createdBy=da5f5248805, createdName=Mr.d, createdTime=Sun Sep 06 11:39:07 CST 2020, time=2020-09-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=882899, encodeId=6db188289958, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=101, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/g?b=oidb&k=DN2yAtxINoWbrXpDEHQs1g&s=100&t=1551532692, createdBy=8a085316034, createdName=小雪123, createdTime=Sat Sep 05 11:05:54 CST 2020, time=2020-09-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=882895, encodeId=f81d88289532, content=学习了!, beContent=null, objectType=article, channel=null, level=null, likeNumber=118, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8f435296195, createdName=ms3000000449926787, createdTime=Sat Sep 05 10:45:49 CST 2020, time=2020-09-05, status=1, ipAttribution=)]
    2020-09-05 小雪123

    学习

    0

  8. [GetPortalCommentsPageByObjectIdResponse(id=2049329, encodeId=72f82049329bc, content=<a href='/topic/show?id=4363e929ad' target=_blank style='color:#2F92EE;'>#Gene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7929, encryptionId=4363e929ad, topicName=Gene)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=63a4277, createdName=cy0324, createdTime=Thu Nov 05 00:27:43 CST 2020, time=2020-11-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2042672, encodeId=d64c20426e2c0, content=<a href='/topic/show?id=999c88014ea' target=_blank style='color:#2F92EE;'>#获得性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88014, encryptionId=999c88014ea, topicName=获得性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d4b7363, createdName=pandamao2010, createdTime=Thu Dec 24 20:27:43 CST 2020, time=2020-12-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1979017, encodeId=bab619e90176f, content=<a href='/topic/show?id=3b90e79787f' target=_blank style='color:#2F92EE;'>#细胞癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77978, encryptionId=3b90e79787f, topicName=细胞癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e457184, createdName=qingting, createdTime=Sun Sep 27 09:27:43 CST 2020, time=2020-09-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=884277, encodeId=07378842e716, content=不错, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e6785205858, createdName=1474c43fm46暂无昵称, createdTime=Thu Sep 10 18:06:43 CST 2020, time=2020-09-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1558200, encodeId=2ee31558200ce, content=<a href='/topic/show?id=2f1c13349e7' target=_blank style='color:#2F92EE;'>#Oncogene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13349, encryptionId=2f1c13349e7, topicName=Oncogene)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=154614942533, createdName=zsyan, createdTime=Mon Sep 07 01:27:43 CST 2020, time=2020-09-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=883077, encodeId=9d158830e774, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200820/a50c79dfbf8443c28d9507e5ed481752/4f3848e242344bd8a14c3db699d30a7b.jpg, createdBy=da5f5248805, createdName=Mr.d, createdTime=Sun Sep 06 11:39:07 CST 2020, time=2020-09-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=882899, encodeId=6db188289958, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=101, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/g?b=oidb&k=DN2yAtxINoWbrXpDEHQs1g&s=100&t=1551532692, createdBy=8a085316034, createdName=小雪123, createdTime=Sat Sep 05 11:05:54 CST 2020, time=2020-09-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=882895, encodeId=f81d88289532, content=学习了!, beContent=null, objectType=article, channel=null, level=null, likeNumber=118, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8f435296195, createdName=ms3000000449926787, createdTime=Sat Sep 05 10:45:49 CST 2020, time=2020-09-05, status=1, ipAttribution=)]
    2020-09-05 ms3000000449926787

    学习了!

    0

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