Cell Death Differ:DYRK2激活HSF1增强对蛋白毒性应激反应的抵抗力并促进三阴性乳腺癌的发生发展

2020-12-07 xiaozeng MedSci原创

大约90%的实体瘤和75%的造血癌表现出一定程度的非整倍性。既往研究显示,在酵母和哺乳动物系统中,非整倍体细胞相比于整倍体细胞适应性更差。细胞会通过蛋白质降解和折叠途径调节失衡的非整倍体,而这些途径的

大约90%的实体瘤和75%的造血癌表现出一定程度的非整倍性。既往研究显示,在酵母和哺乳动物系统中,非整倍体细胞相比于整倍体细胞适应性更差。细胞会通过蛋白质降解和折叠途径调节失衡的非整倍体,而这些途径的正调控因子对于非整倍体细胞的存活至关重要,这些调控因子也可作为潜在的癌症治疗靶点。

为了抵抗上述的蛋白毒性应激反应,癌细胞激活了蛋白毒性应激反应途径,该途径受转录因子HSF1(热休克因子1)的调控。由于目前开发针对诸如HSF1的转录调节因子的抑制剂仍具挑战性,因此鉴定和靶向HSF1的上游调节因子或可成为一种可行的替代治疗策略。

DYRK2影响HSF1靶基因HSP70的表达水平

在该研究中,研究人员证实,在三阴性乳腺癌(TNBC)细胞中,DYRK2能够通过磷酸化HSF1,促进其核稳定性和转录活性。敲除DYRK2能够降低HSF1的活性,并使TNBC细胞对蛋白毒性应激反应致敏。重要的是,在TNBC患者的肿瘤中,DYRK2的表达水平与活跃的HSF1正相关,且与患者的不良预后相关,这也说明DYRK2可以促进TNBC的发生发展。

DYRK2表达水平与HSF1核水平相关,且与TNBC患者的不良预后和肿瘤复发相关

综上,以上的研究结果揭示,DYRK2是HSF1转录的关键调节因子以及TNBC的潜在的治疗靶标。


原始出处:


Moreno, R., Banerjee, S., Jackson, A.W. et al. The stress-responsive kinase DYRK2 activates heat shock factor 1 promoting resistance to proteotoxic stress. Cell Death Differ (02 December 2020).

 

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href='/topic/show?id=7b82915059' target=_blank style='color:#2F92EE;'>#HSF1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9150, encryptionId=7b82915059, topicName=HSF1)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=19ad38, createdName=lq1767, createdTime=Tue Jun 08 05:40:19 CST 2021, time=2021-06-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=911855, encodeId=56bf911855ed, content=不错, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210428/62bd4c426c19405fbe25daed5e303e21/325bee3412d648c38717826432a9bc53.jpg, createdBy=f0305306362, createdName=14879b07m27(暂无昵称), createdTime=Tue Dec 29 10:40:19 CST 2020, time=2020-12-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1962387, encodeId=5eed196238e84, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, 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=Wed Nov 10 07:40:19 CST 2021, time=2021-11-10, status=1, ipAttribution=)]
    2021-05-17 忻雨

    赚积分

    0

  5. 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GetPortalCommentsPageByObjectIdResponse(id=1962387, encodeId=5eed196238e84, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, 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=Wed Nov 10 07:40:19 CST 2021, time=2021-11-10, status=1, ipAttribution=)]
  6. [GetPortalCommentsPageByObjectIdResponse(id=1653857, encodeId=2939165385e3b, content=<a href='/topic/show?id=9e7549289e5' target=_blank style='color:#2F92EE;'>#应激反应#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=49289, encryptionId=9e7549289e5, topicName=应激反应)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2ce824383705, createdName=天堂的云, createdTime=Wed Sep 15 10:40:19 CST 2021, time=2021-09-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1872085, encodeId=1bf618e20857e, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, 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href='/topic/show?id=7b82915059' target=_blank style='color:#2F92EE;'>#HSF1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9150, encryptionId=7b82915059, topicName=HSF1)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=19ad38, createdName=lq1767, createdTime=Tue Jun 08 05:40:19 CST 2021, time=2021-06-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=911855, encodeId=56bf911855ed, content=不错, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210428/62bd4c426c19405fbe25daed5e303e21/325bee3412d648c38717826432a9bc53.jpg, createdBy=f0305306362, createdName=14879b07m27(暂无昵称), createdTime=Tue Dec 29 10:40:19 CST 2020, time=2020-12-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1962387, encodeId=5eed196238e84, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, 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=Wed Nov 10 07:40:19 CST 2021, time=2021-11-10, status=1, ipAttribution=)]
  7. 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GetPortalCommentsPageByObjectIdResponse(id=1962387, encodeId=5eed196238e84, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, 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=Wed Nov 10 07:40:19 CST 2021, time=2021-11-10, status=1, ipAttribution=)]
    2021-10-13 isabellayj
  8. 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href='/topic/show?id=7b82915059' target=_blank style='color:#2F92EE;'>#HSF1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9150, encryptionId=7b82915059, topicName=HSF1)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=19ad38, createdName=lq1767, createdTime=Tue Jun 08 05:40:19 CST 2021, time=2021-06-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=911855, encodeId=56bf911855ed, content=不错, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210428/62bd4c426c19405fbe25daed5e303e21/325bee3412d648c38717826432a9bc53.jpg, createdBy=f0305306362, createdName=14879b07m27(暂无昵称), createdTime=Tue Dec 29 10:40:19 CST 2020, time=2020-12-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1962387, encodeId=5eed196238e84, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, 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=Wed Nov 10 07:40:19 CST 2021, time=2021-11-10, status=1, ipAttribution=)]
    2021-06-08 lq1767
  9. 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GetPortalCommentsPageByObjectIdResponse(id=1962387, encodeId=5eed196238e84, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, 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=Wed Nov 10 07:40:19 CST 2021, time=2021-11-10, status=1, ipAttribution=)]
    2020-12-29 14879b07m27(暂无昵称)

    不错

    0

  10. 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GetPortalCommentsPageByObjectIdResponse(id=1962387, encodeId=5eed196238e84, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, 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=Wed Nov 10 07:40:19 CST 2021, time=2021-11-10, status=1, ipAttribution=)]
    2021-11-10 维他命

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