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J Clin Invest：PTEN/AKT和Hippo/YAP/TAZ通路之间的交叉串扰加速了NAFLD和肝癌的发生

2018-02-07 MedSci MedSci原创

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非酒精性脂肪性肝病（NAFLD）是肝癌的主要危险因素，因此，其预防是一个重要的临床目标。磷酸酶和张力蛋白同源物（PTEN）或蛋白激酶Hippo信号通路的消除分别通过激活AKT或转录调节因子YAP/TAZ诱导肝癌，然而，PTEN/AKT和Hippo/YAP/TAZ通路在肝脏肿瘤发生中的相互干扰的作用目前尚不清楚。本研究发现表明，PTEN和SAV1在肝脏中的缺失加速了小鼠中NAFLD和肝癌的发展。在分

非酒精性脂肪性肝病（NAFLD）是肝癌的主要危险因素，因此，其预防是一个重要的临床目标。磷酸酶和张力蛋白同源物（PTEN）或蛋白激酶Hippo信号通路的消除分别通过激活AKT或转录调节因子YAP/TAZ诱导肝癌，然而，PTEN/AKT和Hippo/YAP/TAZ通路在肝脏肿瘤发生中的相互干扰的作用目前尚不清楚。

本研究发现表明，PTEN和SAV1在肝脏中的缺失加速了小鼠中NAFLD和肝癌的发展。在分子水平上，Pten-/-Sav1-/-小鼠肝脏中YAP/TAZ的激活通过上调胰岛素受体底物2（IRS2）的表达来扩大AKT信号。YAP/TAZ的消除和Hippo途径的激活都能挽救这些表型。高水平的YAP/TAZ表达与人肝细胞癌（HCC）中高水平的IRS2表达相关。此外，使用AKT抑制剂MK-2206或通过AAV-Cas9敲除IRS2成功抑制了Pten-/-Sav1/-小鼠肝脏肿瘤的发生。

因此，我们的研究结果表明，Hippo信号通过调节IRS2表达与AKT信号通路相互作用，从而防止NAFLD和肝癌的发展，并提供证据表明这两种途径之间的交叉串扰加速了NAFLD和肝癌的发生。

原始出处：
 
Jeong SH, Kim HB, et al., Hippo-mediated suppression of IRS2/AKT signaling prevents hepatic steatosis and liver cancer. J Clin Invest. 2018 Feb 5. pii: 95802. doi: 10.1172/JCI95802.

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    2018-04-01 xfpan20

    #Akt#

    0

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    2018-07-26 gujh

    #YAP#

    0

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    2018-09-30 12498e5fm22(暂无昵称)

    #AZ#

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    2018-10-19 lvygwyt2781

    #AFLD#

    0

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    2018-10-10 xiangyuzhou971

    #EST#

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1656163, encodeId=b0c71656163ef, content=<a href='/topic/show?id=f4782246ec' target=_blank style='color:#2F92EE;'>#Akt#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2246, encryptionId=f4782246ec, topicName=Akt)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b8c724776724, createdName=xfpan20, createdTime=Sun Apr 01 21:55:00 CST 2018, time=2018-04-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2081892, encodeId=56dc208189233, content=<a href='/topic/show?id=c2971893397' target=_blank style='color:#2F92EE;'>#YAP#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18933, encryptionId=c2971893397, topicName=YAP)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3333505, createdName=gujh, createdTime=Thu Jul 26 18:55:00 CST 2018, time=2018-07-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1714761, encodeId=013e1e14761ff, content=<a href='/topic/show?id=021230e312' target=_blank style='color:#2F92EE;'>#AZ#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3073, encryptionId=021230e312, topicName=AZ)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9e5031899089, createdName=12498e5fm22(暂无昵称), createdTime=Sun Sep 30 05:55:00 CST 2018, time=2018-09-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2083909, encodeId=7af7208390999, content=<a href='/topic/show?id=d3b820e32c' target=_blank style='color:#2F92EE;'>#AFLD#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2073, encryptionId=d3b820e32c, topicName=AFLD)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=947269, createdName=lvygwyt2781, createdTime=Fri Oct 19 12:55:00 CST 2018, time=2018-10-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2051055, encodeId=f5a82051055de, content=<a href='/topic/show?id=95f8e042dd' target=_blank style='color:#2F92EE;'>#EST#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7042, encryptionId=95f8e042dd, topicName=EST)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e9a6357, createdName=xiangyuzhou971, createdTime=Wed Oct 10 02:55:00 CST 2018, time=2018-10-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1315921, encodeId=a71313159214a, content=<a href='/topic/show?id=134f14834f2' target=_blank style='color:#2F92EE;'>#PTEN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14834, encryptionId=134f14834f2, topicName=PTEN)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3f67438, createdName=xiaogang317, createdTime=Fri Feb 09 10:55:00 CST 2018, time=2018-02-09, status=1, ipAttribution=)]
    2018-02-09 xiaogang317

    #PTEN#

    0

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