Nature Communicaiton：通过HIF-1抑制乳腺癌转移新策略

2015-01-26 佚名生物谷

近日，国际期刊Nature Communication在线发表了日本科学家的一项最新研究成果，发现泛素C端水解酶L1(UCHL1)能够作为HIF-1a的去泛素化酶促进肿瘤转移，表明或许可以利用UCHL1作为肿瘤转移诊断标记和癌症治疗靶点。   HIF-1在肿瘤中转移过程中发挥重要作用，但能够激活HIF-1并进一步促进肿瘤转移的基因仍没有得到鉴定。研究人员发现UCHL1能够减弱VH

近日，国际期刊Nature Communication在线发表了日本科学家的一项最新研究成果，发现泛素C端水解酶L1(UCHL1)能够作为HIF-1a的去泛素化酶促进肿瘤转移，表明或许可以利用UCHL1作为肿瘤转移诊断标记和癌症治疗靶点。

HIF-1在肿瘤中转移过程中发挥重要作用，但能够激活HIF-1并进一步促进肿瘤转移的基因仍没有得到鉴定。研究人员发现UCHL1能够减弱VHL介导的HIF1a泛素化，HIF-1a是HIF-1复合体中非常重要的调控亚基，因此UCHL1通过对HIF-1a的去泛素化作用激活了HIF-1的功能。

在小鼠肿瘤肺转移模型中，UCHL1的异常过表达能够促进HIF-1依赖性的肿瘤长距离转移，同时，阻断UCHL1-HIF1相互作用能够抑制具有转移特性的肿瘤的形成。在乳腺癌和肺癌病人中进一步发现，UCHL1的表达水平与HIF-1a都与病人的不良预后成强烈相关性，并且UCHL1和HIF-1a之间也具有表达水平的相关性。

综上所述，文章发现UCHL1能够对HIF-1调控亚基HIF-1a进行去泛素化，减弱VHL介导的泛素化降解作用，导致HIF-1持续激活下游与肿瘤转移相关的基因，从而导致肿瘤发生转移。鉴于UCHL1表达与肿瘤病人不良预后的相关性，可以将UCHL1开发为肿瘤转移的诊断标记，并针对UCHL1-HIF1之间相互作用设计癌症治疗方案。

原始出处

Goto Y1, Zeng L2, Yeom CJ1, Zhu Y3, Morinibu A1, Shinomiya K1, Kobayashi M1, Hirota K4, Itasaka S5, Yoshimura M5, Tanimoto K6, Torii M7, Sowa T8, Menju T8, Sonobe M8, Kakeya H9, Toi M7, Date H8, Hammond EM10, Hiraoka M5, Harada H11.UCHL1 provides diagnostic and antimetastatic strategies due to its deubiquitinating effect on HIF-1α.Nat Commun. 2015 Jan 23

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2015-04-28 ms6390871039024434

#AIT#

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2015-07-25 liye789132251

#Nat#

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2015-09-24 liuli5079

#COMMUN#

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2015-01-28 12498568m52暂无昵称

#新策略#

30 0
[GetPortalCommentsPageByObjectIdResponse(id=2081941, encodeId=54ad2081941d8, content=<a href='/topic/show?id=35032192c2' target=_blank style='color:#2F92EE;'>#AIT#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2192, encryptionId=35032192c2, topicName=AIT)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTIibticIBly5jCSic5ZElW4He3rO4DMpUHUFaFX57OicNMnzckWaicBNeStwugWHFCuOdicoakApM4HGmtw/132, createdBy=f8672500006, createdName=ms6390871039024434, createdTime=Tue Apr 28 17:18:00 CST 2015, time=2015-04-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1880470, encodeId=149018804e006, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Sat Jul 25 13:18:00 CST 2015, time=2015-07-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2086759, encodeId=37352086e5973, content=<a href='/topic/show?id=490750196b' target=_blank style='color:#2F92EE;'>#COMMUN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5019, encryptionId=490750196b, topicName=COMMUN)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7931272, createdName=liuli5079, createdTime=Thu Sep 24 02:18:00 CST 2015, time=2015-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1478354, encodeId=b2b314e8354db, content=<a href='/topic/show?id=d1a55858e70' target=_blank style='color:#2F92EE;'>#新策略#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58587, encryptionId=d1a55858e70, topicName=新策略)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=da0f7431516, createdName=12498568m52暂无昵称, createdTime=Wed Jan 28 00:18:00 CST 2015, time=2015-01-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1556019, encodeId=015115560195d, content=<a href='/topic/show?id=b3e98813c3' target=_blank style='color:#2F92EE;'>#HIF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8813, encryptionId=b3e98813c3, topicName=HIF)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=293014689254, createdName=wrj0126, createdTime=Wed Jan 28 00:18:00 CST 2015, time=2015-01-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1590260, encodeId=d55a159026058, content=<a href='/topic/show?id=2c17e154824' target=_blank style='color:#2F92EE;'>#癌转移#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=71548, encryptionId=2c17e154824, topicName=癌转移)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2dc017794099, createdName=linagood, createdTime=Wed Jan 28 00:18:00 CST 2015, time=2015-01-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=14720, encodeId=d6a914e202b, content=不靠谱, beContent=null, objectType=article, channel=null, level=null, likeNumber=111, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=223.104.5.**, createdTime=Mon Jan 26 18:14:00 CST 2015, time=2015-01-26, status=1, ipAttribution=)]
2015-01-28 wrj0126

#HIF#

38 0
[GetPortalCommentsPageByObjectIdResponse(id=2081941, encodeId=54ad2081941d8, content=<a href='/topic/show?id=35032192c2' target=_blank style='color:#2F92EE;'>#AIT#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2192, encryptionId=35032192c2, topicName=AIT)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTIibticIBly5jCSic5ZElW4He3rO4DMpUHUFaFX57OicNMnzckWaicBNeStwugWHFCuOdicoakApM4HGmtw/132, createdBy=f8672500006, createdName=ms6390871039024434, createdTime=Tue Apr 28 17:18:00 CST 2015, time=2015-04-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1880470, encodeId=149018804e006, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Sat Jul 25 13:18:00 CST 2015, time=2015-07-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2086759, encodeId=37352086e5973, content=<a href='/topic/show?id=490750196b' target=_blank style='color:#2F92EE;'>#COMMUN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5019, encryptionId=490750196b, topicName=COMMUN)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7931272, createdName=liuli5079, createdTime=Thu Sep 24 02:18:00 CST 2015, time=2015-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1478354, encodeId=b2b314e8354db, content=<a href='/topic/show?id=d1a55858e70' target=_blank style='color:#2F92EE;'>#新策略#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58587, encryptionId=d1a55858e70, topicName=新策略)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=da0f7431516, createdName=12498568m52暂无昵称, createdTime=Wed Jan 28 00:18:00 CST 2015, time=2015-01-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1556019, encodeId=015115560195d, content=<a href='/topic/show?id=b3e98813c3' target=_blank style='color:#2F92EE;'>#HIF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8813, encryptionId=b3e98813c3, topicName=HIF)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=293014689254, createdName=wrj0126, createdTime=Wed Jan 28 00:18:00 CST 2015, time=2015-01-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1590260, encodeId=d55a159026058, content=<a href='/topic/show?id=2c17e154824' target=_blank style='color:#2F92EE;'>#癌转移#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=71548, encryptionId=2c17e154824, topicName=癌转移)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2dc017794099, createdName=linagood, createdTime=Wed Jan 28 00:18:00 CST 2015, time=2015-01-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=14720, encodeId=d6a914e202b, content=不靠谱, beContent=null, objectType=article, channel=null, level=null, likeNumber=111, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=223.104.5.**, createdTime=Mon Jan 26 18:14:00 CST 2015, time=2015-01-26, status=1, ipAttribution=)]
2015-01-28 linagood

#癌转移#

28 0
[GetPortalCommentsPageByObjectIdResponse(id=2081941, encodeId=54ad2081941d8, content=<a href='/topic/show?id=35032192c2' target=_blank style='color:#2F92EE;'>#AIT#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2192, encryptionId=35032192c2, topicName=AIT)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTIibticIBly5jCSic5ZElW4He3rO4DMpUHUFaFX57OicNMnzckWaicBNeStwugWHFCuOdicoakApM4HGmtw/132, createdBy=f8672500006, createdName=ms6390871039024434, createdTime=Tue Apr 28 17:18:00 CST 2015, time=2015-04-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1880470, encodeId=149018804e006, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Sat Jul 25 13:18:00 CST 2015, time=2015-07-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2086759, encodeId=37352086e5973, content=<a href='/topic/show?id=490750196b' target=_blank style='color:#2F92EE;'>#COMMUN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5019, encryptionId=490750196b, topicName=COMMUN)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7931272, createdName=liuli5079, createdTime=Thu Sep 24 02:18:00 CST 2015, time=2015-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1478354, encodeId=b2b314e8354db, content=<a href='/topic/show?id=d1a55858e70' target=_blank style='color:#2F92EE;'>#新策略#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58587, encryptionId=d1a55858e70, topicName=新策略)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=da0f7431516, createdName=12498568m52暂无昵称, createdTime=Wed Jan 28 00:18:00 CST 2015, time=2015-01-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1556019, encodeId=015115560195d, content=<a href='/topic/show?id=b3e98813c3' target=_blank style='color:#2F92EE;'>#HIF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8813, encryptionId=b3e98813c3, topicName=HIF)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=293014689254, createdName=wrj0126, createdTime=Wed Jan 28 00:18:00 CST 2015, time=2015-01-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1590260, encodeId=d55a159026058, content=<a href='/topic/show?id=2c17e154824' target=_blank style='color:#2F92EE;'>#癌转移#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=71548, encryptionId=2c17e154824, topicName=癌转移)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2dc017794099, createdName=linagood, createdTime=Wed Jan 28 00:18:00 CST 2015, time=2015-01-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=14720, encodeId=d6a914e202b, content=不靠谱, beContent=null, objectType=article, channel=null, level=null, likeNumber=111, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=223.104.5.**, createdTime=Mon Jan 26 18:14:00 CST 2015, time=2015-01-26, status=1, ipAttribution=)]
2015-01-26 223.104.5.**

不靠谱

111 0

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