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J Clin Invest：紧密连接蛋白18介导的YAP活性调节肺干和祖细胞稳态和肿瘤发生

2018-02-10 MedSci MedSci原创

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紧密连接蛋白是调节细胞旁通透性和细胞极性的整体紧密连接（TJ）蛋白，通常在癌症中的表达失调，然而它们在肿瘤进展中的作用尚不清楚。本研究中，研究人员发现敲除Cldn18，一种在肺泡上皮中高表达的紧密连接蛋白家族成员，导致肺增大、实质扩张、丰度增加，及远端肺祖细胞、II型肺泡上皮细胞（AT2）的增殖，以及Yes相关蛋白（YAP）的激活，器官大小增加和小鼠肿瘤的发生。 抑制YAP可降低Cldn18-/-

紧密连接蛋白是调节细胞旁通透性和细胞极性的整体紧密连接（TJ）蛋白，通常在癌症中的表达失调，然而它们在肿瘤进展中的作用尚不清楚。

本研究中，研究人员发现敲除Cldn18，一种在肺泡上皮中高表达的紧密连接蛋白家族成员，导致肺增大、实质扩张、丰度增加，及远端肺祖细胞、II型肺泡上皮细胞（AT2）的增殖，以及Yes相关蛋白（YAP）的激活，器官大小增加和小鼠肿瘤的发生。

抑制YAP可降低Cldn18-/-AT2细胞的增殖和集落形成效率（CFE），且抑制了肺大小的增加，而CLDN18过表达则降低了YAP核定位、细胞增殖、CFE和YAP转录活性。CLDN18和YAP在细胞-胞接触时相互作用并共定位，而CLDN18丧失则降低了YAP与Hippo激酶p-LATS1/2的相互作用。此外，Cldn18-/-小鼠随着年龄增长，发展为肺腺癌（LuAd）的倾向性增加，而人LuAd显示CLDN18的阶段依赖性减少。

综上所述，该研究结果表明，CLDN18是限制器官大小、祖细胞增殖和肿瘤发生的YAP活性的调节剂，并且提示TJ中断可以促进祖细胞增殖以增强损伤后修复的机制。

原始出处：

Zhou B, Flodby P, Claudin-18-mediated YAP activity regulates lung stem and progenitor cell homeostasis and tumorigenesis. J Clin Invest. 2018 Feb 5. pii: 90429. doi: 10.1172/JCI90429.

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    2019-01-15 xiangyuzhou971

    #EST#

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=2051058, encodeId=06a4205105881, content=<a href='/topic/show?id=95f8e042dd' target=_blank style='color:#2F92EE;'>#EST#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7042, encryptionId=95f8e042dd, topicName=EST)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e9a6357, createdName=xiangyuzhou971, createdTime=Tue Jan 15 06:04:00 CST 2019, time=2019-01-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2076119, encodeId=554620e611905, content=<a href='/topic/show?id=abf6945365f' target=_blank style='color:#2F92EE;'>#连接蛋白#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=94536, encryptionId=abf6945365f, topicName=连接蛋白)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6393434, createdName=ailian1202, createdTime=Sat Dec 08 06:04:00 CST 2018, time=2018-12-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2081897, encodeId=13d7208189e46, content=<a href='/topic/show?id=c2971893397' target=_blank style='color:#2F92EE;'>#YAP#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18933, encryptionId=c2971893397, topicName=YAP)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3333505, createdName=gujh, createdTime=Fri Sep 21 10:04:00 CST 2018, time=2018-09-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1646717, encodeId=b7d81646e17c8, content=<a href='/topic/show?id=4478e5315e1' target=_blank style='color:#2F92EE;'>#稳态#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=75315, encryptionId=4478e5315e1, topicName=稳态)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3ebc23344390, createdName=changfy, createdTime=Thu Oct 25 08:04:00 CST 2018, time=2018-10-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1512439, encodeId=ebfe151243993, content=<a href='/topic/show?id=f802e4102cb' target=_blank style='color:#2F92EE;'>#祖细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=74102, encryptionId=f802e4102cb, topicName=祖细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f18310470858, createdName=12498636m52(暂无昵称), createdTime=Mon Feb 12 12:04:00 CST 2018, time=2018-02-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=286878, encodeId=d9492868e82e, content=不错的文章值得拥有, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=eff51996281, createdName=1e1b8538m79(暂无匿称), createdTime=Sat Feb 10 22:16:47 CST 2018, time=2018-02-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=286868, encodeId=3b1f28686852, content=学习谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3zMoyicyo6ia9f4IuLQAwZoxD6Hx4ibd5CMcOCYhStY6oDibbKK6O2X8iaicldO5ib8j1iapOIobIKCGiczU2A/0, createdBy=56251941490, createdName=虈亣靌, createdTime=Sat Feb 10 22:11:08 CST 2018, time=2018-02-10, status=1, ipAttribution=)]
    2018-12-08 ailian1202

    #连接蛋白#

    0

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    2018-09-21 gujh

    #YAP#

    0

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    2018-10-25 changfy

    #稳态#

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=2051058, encodeId=06a4205105881, content=<a href='/topic/show?id=95f8e042dd' target=_blank style='color:#2F92EE;'>#EST#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7042, encryptionId=95f8e042dd, topicName=EST)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e9a6357, createdName=xiangyuzhou971, createdTime=Tue Jan 15 06:04:00 CST 2019, time=2019-01-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2076119, encodeId=554620e611905, content=<a href='/topic/show?id=abf6945365f' target=_blank style='color:#2F92EE;'>#连接蛋白#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=94536, encryptionId=abf6945365f, topicName=连接蛋白)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6393434, createdName=ailian1202, createdTime=Sat Dec 08 06:04:00 CST 2018, time=2018-12-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2081897, encodeId=13d7208189e46, content=<a href='/topic/show?id=c2971893397' target=_blank style='color:#2F92EE;'>#YAP#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18933, encryptionId=c2971893397, topicName=YAP)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3333505, createdName=gujh, createdTime=Fri Sep 21 10:04:00 CST 2018, time=2018-09-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1646717, encodeId=b7d81646e17c8, content=<a href='/topic/show?id=4478e5315e1' target=_blank style='color:#2F92EE;'>#稳态#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=75315, encryptionId=4478e5315e1, topicName=稳态)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3ebc23344390, createdName=changfy, createdTime=Thu Oct 25 08:04:00 CST 2018, time=2018-10-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1512439, encodeId=ebfe151243993, content=<a href='/topic/show?id=f802e4102cb' target=_blank style='color:#2F92EE;'>#祖细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=74102, encryptionId=f802e4102cb, topicName=祖细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f18310470858, createdName=12498636m52(暂无昵称), createdTime=Mon Feb 12 12:04:00 CST 2018, time=2018-02-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=286878, encodeId=d9492868e82e, content=不错的文章值得拥有, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=eff51996281, createdName=1e1b8538m79(暂无匿称), createdTime=Sat Feb 10 22:16:47 CST 2018, time=2018-02-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=286868, encodeId=3b1f28686852, content=学习谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3zMoyicyo6ia9f4IuLQAwZoxD6Hx4ibd5CMcOCYhStY6oDibbKK6O2X8iaicldO5ib8j1iapOIobIKCGiczU2A/0, createdBy=56251941490, createdName=虈亣靌, createdTime=Sat Feb 10 22:11:08 CST 2018, time=2018-02-10, status=1, ipAttribution=)]
    2018-02-12 12498636m52(暂无昵称)

    #祖细胞#

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=2051058, encodeId=06a4205105881, content=<a href='/topic/show?id=95f8e042dd' target=_blank style='color:#2F92EE;'>#EST#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7042, encryptionId=95f8e042dd, topicName=EST)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e9a6357, createdName=xiangyuzhou971, createdTime=Tue Jan 15 06:04:00 CST 2019, time=2019-01-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2076119, encodeId=554620e611905, content=<a href='/topic/show?id=abf6945365f' target=_blank style='color:#2F92EE;'>#连接蛋白#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=94536, encryptionId=abf6945365f, topicName=连接蛋白)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6393434, createdName=ailian1202, createdTime=Sat Dec 08 06:04:00 CST 2018, time=2018-12-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2081897, encodeId=13d7208189e46, content=<a href='/topic/show?id=c2971893397' target=_blank style='color:#2F92EE;'>#YAP#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18933, encryptionId=c2971893397, topicName=YAP)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3333505, createdName=gujh, createdTime=Fri Sep 21 10:04:00 CST 2018, time=2018-09-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1646717, encodeId=b7d81646e17c8, content=<a href='/topic/show?id=4478e5315e1' target=_blank style='color:#2F92EE;'>#稳态#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=75315, encryptionId=4478e5315e1, topicName=稳态)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3ebc23344390, createdName=changfy, createdTime=Thu Oct 25 08:04:00 CST 2018, time=2018-10-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1512439, encodeId=ebfe151243993, content=<a href='/topic/show?id=f802e4102cb' target=_blank style='color:#2F92EE;'>#祖细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=74102, encryptionId=f802e4102cb, topicName=祖细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f18310470858, createdName=12498636m52(暂无昵称), createdTime=Mon Feb 12 12:04:00 CST 2018, time=2018-02-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=286878, encodeId=d9492868e82e, content=不错的文章值得拥有, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=eff51996281, createdName=1e1b8538m79(暂无匿称), createdTime=Sat Feb 10 22:16:47 CST 2018, time=2018-02-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=286868, encodeId=3b1f28686852, content=学习谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3zMoyicyo6ia9f4IuLQAwZoxD6Hx4ibd5CMcOCYhStY6oDibbKK6O2X8iaicldO5ib8j1iapOIobIKCGiczU2A/0, createdBy=56251941490, createdName=虈亣靌, createdTime=Sat Feb 10 22:11:08 CST 2018, time=2018-02-10, status=1, ipAttribution=)]
    2018-02-10 1e1b8538m79(暂无匿称)

    不错的文章值得拥有

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=2051058, encodeId=06a4205105881, content=<a href='/topic/show?id=95f8e042dd' target=_blank style='color:#2F92EE;'>#EST#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7042, encryptionId=95f8e042dd, topicName=EST)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e9a6357, createdName=xiangyuzhou971, createdTime=Tue Jan 15 06:04:00 CST 2019, time=2019-01-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2076119, encodeId=554620e611905, content=<a href='/topic/show?id=abf6945365f' target=_blank style='color:#2F92EE;'>#连接蛋白#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=94536, encryptionId=abf6945365f, topicName=连接蛋白)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6393434, createdName=ailian1202, createdTime=Sat Dec 08 06:04:00 CST 2018, time=2018-12-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2081897, encodeId=13d7208189e46, content=<a href='/topic/show?id=c2971893397' target=_blank style='color:#2F92EE;'>#YAP#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18933, encryptionId=c2971893397, topicName=YAP)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3333505, createdName=gujh, createdTime=Fri Sep 21 10:04:00 CST 2018, time=2018-09-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1646717, encodeId=b7d81646e17c8, content=<a href='/topic/show?id=4478e5315e1' target=_blank style='color:#2F92EE;'>#稳态#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=75315, encryptionId=4478e5315e1, topicName=稳态)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3ebc23344390, createdName=changfy, createdTime=Thu Oct 25 08:04:00 CST 2018, time=2018-10-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1512439, encodeId=ebfe151243993, content=<a href='/topic/show?id=f802e4102cb' target=_blank style='color:#2F92EE;'>#祖细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=74102, encryptionId=f802e4102cb, topicName=祖细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f18310470858, createdName=12498636m52(暂无昵称), createdTime=Mon Feb 12 12:04:00 CST 2018, time=2018-02-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=286878, encodeId=d9492868e82e, content=不错的文章值得拥有, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=eff51996281, createdName=1e1b8538m79(暂无匿称), createdTime=Sat Feb 10 22:16:47 CST 2018, time=2018-02-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=286868, encodeId=3b1f28686852, content=学习谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3zMoyicyo6ia9f4IuLQAwZoxD6Hx4ibd5CMcOCYhStY6oDibbKK6O2X8iaicldO5ib8j1iapOIobIKCGiczU2A/0, createdBy=56251941490, createdName=虈亣靌, createdTime=Sat Feb 10 22:11:08 CST 2018, time=2018-02-10, status=1, ipAttribution=)]
    2018-02-10 虈亣靌

    学习谢谢分享

    0

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