NAT COMMUN:中科院詹丽杏研究组发现三阴性乳腺癌治疗新靶标

2018-08-30 细胞中国科学院

国际学术期刊Nature Communication在线发表了中国科学院上海生命科学研究院（营养与健康院）詹丽杏研究组的研究成果“Loss of Wwox drives metastasis in triple-negative breast cancer by JAK2/STAT3 axis”。该研究分析了三阴性乳腺癌患者的转录组特征，发现经典的IL6/JAK2/STAT3通路以及下游信号在三阴

国际学术期刊Nature Communication在线发表了中国科学院上海生命科学研究院（营养与健康院）詹丽杏研究组的研究成果“Loss of Wwox drives metastasis in triple-negative breast cancer by JAK2/STAT3 axis”。该研究分析了三阴性乳腺癌患者的转录组特征，发现经典的IL6/JAK2/STAT3通路以及下游信号在三阴性乳腺癌中呈异常持续激活状态，发现并确认了乳腺癌中JAK2/STAT3信号的新抑制子Wwox蛋白，阐明Wwox的异常减弱和JAK2/STAT3的异常激活这样的负相关关系是高度恶性三阴性乳腺癌发生转移的重要原因。

雌激素受体(ER)、孕激素受体(PR)和人表皮生长因子受体2(Her-2)均为阴性的一种乳腺癌亚型。三阴性乳腺癌侵袭力极强，远处转移风险大，预后极差。目前三阴性乳腺癌治疗手段比较单一，以化疗为主，极易复发和转移。与其他类型乳腺癌相比，内分泌治疗和分子靶向治疗对三阴性乳腺癌均无效。如何为三阴性乳腺癌患者带来更好的诊断手段和个性化治疗选择仍然是研究人员关注的重要问题。

带着这一科学问题，詹丽杏组的研究人员筛选了三阴性乳腺癌细胞与正常乳腺细胞进行了转录组学分析，获得IL6/JAK2/STAT3通路多个信号的异常表达特征。进一步采用人类细胞因子抗体芯片技术和体内体外模型，证明了三阴性乳腺癌细胞的IL6高度异常表达以及其激活的JAK2/STAT3的持续活化可能是三阴性乳腺癌发生远端转移的重要因素。研究中还发现，此前被认为的JAK2/STAT3的主要抑制因子SOCS3并未在三阴性乳腺癌中发挥其抑制作用；而williamhill asia 新发现的脆性位点基因Wwox则在乳腺癌发生IL6/JAK2/STAT3信号通路持续活化过程中产生特异性抑制作用。通过采用NIH3T3/STAT3CA细胞模型，williamhill asia 验证了Wwox对体内持续STAT3信号高磷酸化水平以及持续活化状态的抑制作用。此外结合双荧光素酶报告基因法EMSA以及CHIP实验，williamhill asia 进一步验证了Wwox蛋白可以抑制p-STAT3结合到IL-6启动子区域从而抑制IL-6蛋白高表达。Wwox已被证实位于人类基因组中的常见型脆性位点（Common fragile sites，CFSs），CFSs易于发生断裂，从而影响相关功能基因的编码。以往多篇文献证明了Wwox在包括乳腺癌等多种肿瘤中的异常低表达。而williamhill asia 基于体内体外以及临床证据的研究证明相比其他类型乳腺癌，Wwox在三阴性乳腺癌中显着低表达，且与IL6/JAK2/STAT3异常持续活化呈负相关关系。williamhill asia 的研究首次证明了Wwox对肿瘤细胞JAK2/STAT3高磷酸化和持续活化的强抑制作用，而Wwox的作用机制有望为三阴性乳腺癌的个体化治疗提供靶点和线索。

本研究由博士研究生常人绪等在詹丽杏研究员的指导下完成，也得到了以色列希伯来大学的Rami I. Aqeilan教授、卢森堡大学Claude Haan教授、中科院上海生化细胞所王纲研究员的帮助。同时，本研究得到国家自然科学基金委，科技部以及中科院药物先导等项目的共同资助以及上海营养与健康院公共技术平台的支持。

原始出处：

Renxu Chang, Lele Song, Yi Xu, Yanjun Wu, et al.Loss of Wwox drives metastasis in triple-negative breast cancer by JAK2/STAT3 axis.Nature Communicationsvolume 9, Article number: 3486 (2018)| Published: 28 August 2018

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2019-01-23 gous

#中科院#

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2018-10-05 liuli5079

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objectType=article, channel=null, level=null, likeNumber=107, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=086b2430814, createdName=努力中的小任性, createdTime=Fri Aug 31 04:56:22 CST 2018, time=2018-08-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=341828, encodeId=e19d341828b8, content=了解一下，谢谢分享！, beContent=null, objectType=article, channel=null, level=null, likeNumber=121, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/12/23/2f51002e1349ccda5be11c1eea1e1e60.jpg, createdBy=a22097948, createdName=天地飞扬, createdTime=Thu Aug 30 22:11:21 CST 2018, time=2018-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=341821, encodeId=abfb34182182, content=学习了，谢谢分享。, beContent=null, objectType=article, channel=null, level=null, likeNumber=104, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/xkvRjYnJzzRJ2R0y7VhicibvkjPWHjIMmu4ZpKnE9cWAu4lVicS3uDUCfF4M4JWvrkrYfpb2KehPV0Ee29tPqyPEebBUibiaKhnvD/0, createdBy=f8412001184, createdName=惠映实验室, createdTime=Thu Aug 30 22:10:00 CST 2018, time=2018-08-30, status=1, ipAttribution=)]
2018-09-06 circumcision

#阴性乳腺癌#

72 0
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encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Fri Jul 05 13:01:00 CST 2019, time=2019-07-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1352816, encodeId=80e8135281696, content=<a href='/topic/show?id=827d9996311' target=_blank style='color:#2F92EE;'>#靶标#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99963, encryptionId=827d9996311, topicName=靶标)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Sat Sep 01 13:01:00 CST 2018, time=2018-09-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1458710, encodeId=bed01458e10b8, content=<a href='/topic/show?id=3ef91982030' target=_blank style='color:#2F92EE;'>#三阴性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=19820, encryptionId=3ef91982030, topicName=三阴性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a5666112721, createdName=xlysu, createdTime=Sat Sep 01 13:01:00 CST 2018, time=2018-09-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=341905, encodeId=cd4734190572, content=学习了谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=116, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLbTp9nZtjwVrSZNxAXbAicnKQWnic2eBdJUQYhxO36XdkstSicr7FVF8p5ReH4omtmsbnLdvZLiaJJ1A/132, createdBy=8bff2327056, createdName=kafei, createdTime=Fri Aug 31 07:05:16 CST 2018, time=2018-08-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=341860, encodeId=2371341860d1, content=谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=107, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=086b2430814, createdName=努力中的小任性, createdTime=Fri Aug 31 04:56:22 CST 2018, time=2018-08-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=341828, encodeId=e19d341828b8, content=了解一下，谢谢分享！, beContent=null, objectType=article, channel=null, level=null, likeNumber=121, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/12/23/2f51002e1349ccda5be11c1eea1e1e60.jpg, createdBy=a22097948, createdName=天地飞扬, createdTime=Thu Aug 30 22:11:21 CST 2018, time=2018-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=341821, encodeId=abfb34182182, content=学习了，谢谢分享。, beContent=null, objectType=article, channel=null, level=null, likeNumber=104, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/xkvRjYnJzzRJ2R0y7VhicibvkjPWHjIMmu4ZpKnE9cWAu4lVicS3uDUCfF4M4JWvrkrYfpb2KehPV0Ee29tPqyPEebBUibiaKhnvD/0, createdBy=f8412001184, createdName=惠映实验室, createdTime=Thu Aug 30 22:10:00 CST 2018, time=2018-08-30, status=1, ipAttribution=)]
2019-07-05 liye789132251

#Nat#

83 0
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createdName=liuli5079, createdTime=Fri Oct 05 19:01:00 CST 2018, time=2018-10-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2047989, encodeId=4041204e989ae, content=<a href='/topic/show?id=12e49e53102' target=_blank style='color:#2F92EE;'>#阴性乳腺癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97531, encryptionId=12e49e53102, topicName=阴性乳腺癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f65b226, createdName=circumcision, createdTime=Thu Sep 06 11:01:00 CST 2018, time=2018-09-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1883283, encodeId=d257188328396, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=83, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Fri Jul 05 13:01:00 CST 2019, time=2019-07-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1352816, encodeId=80e8135281696, content=<a href='/topic/show?id=827d9996311' target=_blank style='color:#2F92EE;'>#靶标#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99963, encryptionId=827d9996311, topicName=靶标)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Sat Sep 01 13:01:00 CST 2018, time=2018-09-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1458710, encodeId=bed01458e10b8, content=<a href='/topic/show?id=3ef91982030' target=_blank style='color:#2F92EE;'>#三阴性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=19820, encryptionId=3ef91982030, topicName=三阴性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a5666112721, createdName=xlysu, createdTime=Sat Sep 01 13:01:00 CST 2018, time=2018-09-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=341905, encodeId=cd4734190572, content=学习了谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=116, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLbTp9nZtjwVrSZNxAXbAicnKQWnic2eBdJUQYhxO36XdkstSicr7FVF8p5ReH4omtmsbnLdvZLiaJJ1A/132, createdBy=8bff2327056, createdName=kafei, createdTime=Fri Aug 31 07:05:16 CST 2018, time=2018-08-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=341860, encodeId=2371341860d1, content=谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=107, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=086b2430814, createdName=努力中的小任性, createdTime=Fri Aug 31 04:56:22 CST 2018, time=2018-08-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=341828, encodeId=e19d341828b8, content=了解一下，谢谢分享！, beContent=null, objectType=article, channel=null, level=null, likeNumber=121, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/12/23/2f51002e1349ccda5be11c1eea1e1e60.jpg, createdBy=a22097948, createdName=天地飞扬, createdTime=Thu Aug 30 22:11:21 CST 2018, time=2018-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=341821, encodeId=abfb34182182, content=学习了，谢谢分享。, beContent=null, objectType=article, channel=null, level=null, likeNumber=104, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/xkvRjYnJzzRJ2R0y7VhicibvkjPWHjIMmu4ZpKnE9cWAu4lVicS3uDUCfF4M4JWvrkrYfpb2KehPV0Ee29tPqyPEebBUibiaKhnvD/0, createdBy=f8412001184, createdName=惠映实验室, createdTime=Thu Aug 30 22:10:00 CST 2018, time=2018-08-30, status=1, ipAttribution=)]
2018-09-01 zhaojie88

#靶标#

60 0
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encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Fri Jul 05 13:01:00 CST 2019, time=2019-07-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1352816, encodeId=80e8135281696, content=<a href='/topic/show?id=827d9996311' target=_blank style='color:#2F92EE;'>#靶标#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99963, encryptionId=827d9996311, topicName=靶标)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Sat Sep 01 13:01:00 CST 2018, time=2018-09-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1458710, encodeId=bed01458e10b8, content=<a href='/topic/show?id=3ef91982030' target=_blank style='color:#2F92EE;'>#三阴性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=19820, encryptionId=3ef91982030, topicName=三阴性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a5666112721, createdName=xlysu, createdTime=Sat Sep 01 13:01:00 CST 2018, time=2018-09-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=341905, encodeId=cd4734190572, content=学习了谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=116, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLbTp9nZtjwVrSZNxAXbAicnKQWnic2eBdJUQYhxO36XdkstSicr7FVF8p5ReH4omtmsbnLdvZLiaJJ1A/132, createdBy=8bff2327056, createdName=kafei, createdTime=Fri Aug 31 07:05:16 CST 2018, time=2018-08-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=341860, encodeId=2371341860d1, content=谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=107, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=086b2430814, createdName=努力中的小任性, createdTime=Fri Aug 31 04:56:22 CST 2018, time=2018-08-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=341828, encodeId=e19d341828b8, content=了解一下，谢谢分享！, beContent=null, objectType=article, channel=null, level=null, likeNumber=121, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/12/23/2f51002e1349ccda5be11c1eea1e1e60.jpg, createdBy=a22097948, createdName=天地飞扬, createdTime=Thu Aug 30 22:11:21 CST 2018, time=2018-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=341821, encodeId=abfb34182182, content=学习了，谢谢分享。, beContent=null, objectType=article, channel=null, level=null, likeNumber=104, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/xkvRjYnJzzRJ2R0y7VhicibvkjPWHjIMmu4ZpKnE9cWAu4lVicS3uDUCfF4M4JWvrkrYfpb2KehPV0Ee29tPqyPEebBUibiaKhnvD/0, createdBy=f8412001184, createdName=惠映实验室, createdTime=Thu Aug 30 22:10:00 CST 2018, time=2018-08-30, status=1, ipAttribution=)]
2018-09-01 xlysu

#三阴性#

79 0
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2018-08-31 kafei

学习了谢谢

116 0
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2018-08-31 努力中的小任性

谢谢分享

107 0
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2018-08-30 天地飞扬

了解一下，谢谢分享！

121 0
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level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=19820, encryptionId=3ef91982030, topicName=三阴性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a5666112721, createdName=xlysu, createdTime=Sat Sep 01 13:01:00 CST 2018, time=2018-09-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=341905, encodeId=cd4734190572, content=学习了谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=116, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLbTp9nZtjwVrSZNxAXbAicnKQWnic2eBdJUQYhxO36XdkstSicr7FVF8p5ReH4omtmsbnLdvZLiaJJ1A/132, createdBy=8bff2327056, createdName=kafei, createdTime=Fri Aug 31 07:05:16 CST 2018, time=2018-08-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=341860, encodeId=2371341860d1, content=谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=107, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=086b2430814, createdName=努力中的小任性, createdTime=Fri Aug 31 04:56:22 CST 2018, time=2018-08-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=341828, encodeId=e19d341828b8, content=了解一下，谢谢分享！, beContent=null, objectType=article, channel=null, level=null, likeNumber=121, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/12/23/2f51002e1349ccda5be11c1eea1e1e60.jpg, createdBy=a22097948, createdName=天地飞扬, createdTime=Thu Aug 30 22:11:21 CST 2018, time=2018-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=341821, encodeId=abfb34182182, content=学习了，谢谢分享。, beContent=null, objectType=article, channel=null, level=null, likeNumber=104, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/xkvRjYnJzzRJ2R0y7VhicibvkjPWHjIMmu4ZpKnE9cWAu4lVicS3uDUCfF4M4JWvrkrYfpb2KehPV0Ee29tPqyPEebBUibiaKhnvD/0, createdBy=f8412001184, createdName=惠映实验室, createdTime=Thu Aug 30 22:10:00 CST 2018, time=2018-08-30, status=1, ipAttribution=)]
2018-08-30 惠映实验室

学习了，谢谢分享。

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