Nature：代谢与肿瘤— —糖尿病治疗药物也可治肿瘤

2015-01-30 佚名生物谷

近日，国际顶尖期刊nature刊登了来自美国安德森癌症研究中心Elsa R. Flores研究小组关于IAPP驱动代谢重编程抑制p53缺失的肿瘤生长的最新研究发现。研究人员指出，在人类肿瘤中通常会发生TP53的改变，之前研究也已证明，在小鼠中重新激活TP53能够抑制肿瘤生长。但事实证明，重激活TP53这一策略非常难以实施，因此研究人员试图通过调控TP53同家族蛋白TP63和TP73寻找另外一条

近日，国际顶尖期刊nature刊登了来自美国安德森癌症研究中心Elsa R. Flores研究小组关于IAPP驱动代谢重编程抑制p53缺失的肿瘤生长的最新研究发现。

研究人员指出，在人类肿瘤中通常会发生TP53的改变，之前研究也已证明，在小鼠中重新激活TP53能够抑制肿瘤生长。但事实证明，重激活TP53这一策略非常难以实施，因此研究人员试图通过调控TP53同家族蛋白TP63和TP73寻找另外一条抑制肿瘤生长的策略。p63和p73的TA亚型在结构和功能上都与p53非常类似，但p63和p73的ΔN亚型（缺失酸性转激活结构域）通常在癌症中出现过表达，主要以p53，TA63和TA73的功能缺失形式抑制他们的抗肿瘤功能。p53家族蛋白能广泛影响细胞内各种进程发挥抑制肿瘤的功能，比如细胞凋亡和自噬，因此了解p53家族蛋白与各个细胞过程之间的相互作用对通过改变p53信号通路治疗肿瘤具有重要意义。

Avinashnarayan Venkatanarayan等研究人员通过p63或p73 ΔN亚型缺失发现这会导致细胞内代谢重编程，并且会通过上调IAPP抑制p53缺失的肿瘤生长。IAPP能够编码淀粉不溶素，并通过降钙素受体(CalcR)以及受体活性修饰蛋白3（RAMP3）抑制细胞糖酵解，诱导ROS产生和细胞凋亡。同时，研究人员还发现普兰林肽（目前用于治疗I型和II型糖尿病的药物）能够引起p53缺失的胸腺淋巴瘤的快速抑制。

综上所述，该文章发现p53同家族蛋白p63和p73的ΔN亚型缺失能够上调IAPP表达，驱动肿瘤细胞内代谢重编程，通过诱导ROS产生以及细胞凋亡过程抑制p53缺失的肿瘤生长，同时还发现普兰林肽在抑制胸腺淋巴瘤方面的新作用，这对开发治疗肿瘤新药有非常重要的意义。

原始出处

Venkatanarayan A1, Raulji P2, Norton W3, Chakravarti D1, Coarfa C4, Su X5, Sandur SK6, Ramirez MS7, Lee J7, Kingsley CV7, Sananikone EF1, Rajapakshe K4, Naff K3, Parker-Thornburg J8, Bankson JA7, Tsai KY9, Gunaratne PH10, Flores ER1.IAPP-driven metabolic reprogramming induces regression of p53-deficient tumours in vivo.Nature. 2015 Jan 29

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2015-03-15 zhanglin3079

#糖尿病治疗#

67 0
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2015-02-19 liye789132251

#Nat#

67 0
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2015-09-20 docwu2019

#治疗药物#

59 0
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2015-04-11 x35042875

AKI对心衰临床治疗意义重大，但依然需要研究检验其适用性

131 0
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2015-02-17 chinayinhan

已阅

158 0
[GetPortalCommentsPageByObjectIdResponse(id=1989924, encodeId=163b19899245a, content=<a href='/topic/show?id=3207e6735ae' target=_blank style='color:#2F92EE;'>#糖尿病治疗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76735, encryptionId=3207e6735ae, topicName=糖尿病治疗)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e6a1280, createdName=zhanglin3079, createdTime=Sun Mar 15 05:39:00 CST 2015, time=2015-03-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1880475, encodeId=63b118804e550, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Thu Feb 19 08:39:00 CST 2015, time=2015-02-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1921619, encodeId=e4941921619dc, content=<a href='/topic/show?id=4f0a6469837' target=_blank style='color:#2F92EE;'>#治疗药物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64698, encryptionId=4f0a6469837, topicName=治疗药物)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=docwu2019, createdTime=Sun Sep 20 16:39:00 CST 2015, time=2015-09-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=20403, encodeId=7a9c2040384, content=AKI对心衰临床治疗意义重大，但依然需要研究检验其适用性, beContent=null, objectType=article, channel=null, level=null, likeNumber=131, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20150920/IMG55FDE671A89482379.jpg, createdBy=cef3108336, createdName=x35042875, createdTime=Sat Apr 11 22:49:00 CST 2015, time=2015-04-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=16275, encodeId=0a92162e536, content=已阅, beContent=null, objectType=article, channel=null, level=null, likeNumber=158, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=da6b7222, createdName=chinayinhan, createdTime=Tue Feb 17 01:08:00 CST 2015, time=2015-02-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=14889, encodeId=967a14889a1, content=双胍！, beContent=null, objectType=article, channel=null, level=null, likeNumber=188, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c4a5105539, createdName=lovetcm, createdTime=Fri Jan 30 19:57:00 CST 2015, time=2015-01-30, status=1, ipAttribution=)]
2015-01-30 lovetcm

双胍！

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Nature：代谢与肿瘤— —糖尿病治疗药物也可治肿瘤

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