Nat Cell Bio：Rho GTP酶新功能--抑制乳腺肿瘤生成以及皮-间质细胞转化

2015-01-19 佚名生物谷

通过生物信息学分析，研究者们发现基底样和三阴性乳腺癌中Rho GTP酶Rnd1是一个潜在的肿瘤转移抑制因子。敲除Rnd1蛋白破坏了上皮细胞的粘连和极性，导致上皮-间质细胞转化的发生，同时胞内的c-Myc表达发生紊乱、肿瘤抑制因子p53受到抑制，也导致了细胞产生肿瘤化转变。机制研究显示Rnd1通过激活PlexinB1蛋白的GAP结构域抑制Ras信号的传导，从而抑制Rap1的功能。而在乳腺上皮细胞中抑

通过生物信息学分析，研究者们发现基底样和三阴性乳腺癌中Rho GTP酶Rnd1是一个潜在的肿瘤转移抑制因子。敲除Rnd1蛋白破坏了上皮细胞的粘连和极性，导致上皮-间质细胞转化的发生，同时胞内的c-Myc表达发生紊乱、肿瘤抑制因子p53受到抑制，也导致了细胞产生肿瘤化转变。

机制研究显示Rnd1通过激活PlexinB1蛋白的GAP结构域抑制Ras信号的传导，从而抑制Rap1的功能。而在乳腺上皮细胞中抑制Rap1会导致小鼠长出未分化但浸润性高的肿瘤。相反的，Rnd1的正常表达能够压制小鼠乳腺癌的自发性肺部转移。基因组学研究数据表明人类乳腺癌组织中RND1基因的功能受到抑制，主要机制是通过表观遗传学沉默，或极罕见的点突变造成该基因被删除。这些实验结果向我们揭示了之前未曾想见的乳腺癌发生发展机制--Rnd1限制了Ras-MAPK信号通路。

或许这个Rho GTP酶家族的新成员能为乳腺癌治疗提供新的药物开发靶点。

原始出处

Tomoyo Okada, Surajit Sinha, Ilaria Esposito, Gaia Schiavon.The Rho GTPase Rnd1 suppresses mammary tumorigenesis and EMT by restraining Ras-MAPK signalling.Nature Cell Biology.2014

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2015-10-24 ms9608593228839890

#新功能#

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2015-07-24 yangpeizhi

#乳腺肿瘤#

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2015-09-30 liye789132251

#Nat#

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2015-08-07 sunylz

#Bio#

25 0
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2015-02-07 zhaozhouchifen

#Cell#

28 0
[GetPortalCommentsPageByObjectIdResponse(id=1923889, encodeId=db5f19238898c, content=<a href='/topic/show?id=002658104e8' target=_blank style='color:#2F92EE;'>#新功能#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58104, encryptionId=002658104e8, topicName=新功能)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/L2dMhrxjvSWuPWKZZP1I83Rw21EWia7LVTYJibLQkb4oTibrYLwhnAXntTBWR3FruIzKfNMiaBwhYV0AKNmiaNxfialg/132, createdBy=6ea92500119, createdName=ms9608593228839890, createdTime=Sat Oct 24 07:19:00 CST 2015, time=2015-10-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2028096, encodeId=c523202809621, content=<a href='/topic/show?id=096123e95c5' target=_blank style='color:#2F92EE;'>#乳腺肿瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=23795, encryptionId=096123e95c5, topicName=乳腺肿瘤)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ec25412, createdName=yangpeizhi, createdTime=Fri Jul 24 04:19:00 CST 2015, time=2015-07-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1880462, encodeId=0bb518804629f, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Wed Sep 30 14:19:00 CST 2015, time=2015-09-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1917120, encodeId=7ea1191e12063, content=<a href='/topic/show?id=4f26341994' target=_blank style='color:#2F92EE;'>#Bio#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3419, encryptionId=4f26341994, topicName=Bio)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=12de429, createdName=sunylz, createdTime=Fri Aug 07 22:19:00 CST 2015, time=2015-08-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1868996, encodeId=2f681868996a9, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Sat Feb 07 09:19:00 CST 2015, time=2015-02-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1959247, encodeId=6c75195924e54, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, 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=Mon Sep 21 19:19:00 CST 2015, time=2015-09-21, status=1, ipAttribution=)]
2015-09-21 维他命

#CEL#

28 0

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