AUTOPHAGY:自噬促进肿瘤代谢重编程

2018-07-03 海北 MedSci原创

尽管我们对巨自噬/自噬的促存活作用有了一定的了解,但是由于自噬受损引起的营养缺乏如何影响致癌KRAS驱动的肿瘤进展却知之甚少。

基底自噬的缺陷限制了细胞内成分再循环的营养供应。尽管我们对巨自噬/自噬的促存活作用有了一定的了解,但是由于自噬受损引起的营养缺乏如何影响致癌KRAS驱动的肿瘤进展却知之甚少。
最近,来自美国的研究人员证明,自噬基因Atg5的条件性敲除(atg5-KO)将KRASG12V驱动的荷瘤小鼠的存活延长了38%。尽管发病较快,但atg5-KO肿瘤在晚期肿瘤发生过程中传播较慢。 atg5-KO肿瘤细胞显示出线粒体功能降低和线粒体断裂增加。
尽管ASNS(天冬酰胺合成酶),天然天冬酰胺合成的关键酶,出现了补偿性过表达,代谢物谱显示非必需氨基酸天冬酰胺出现了缺乏。自噬或ASNS的抑制减少了KRASG12V驱动的肿瘤细胞增殖,迁移和侵袭,其可以通过天冬酰胺补充或敲除MFF(线粒体裂变因子)来挽救。
最后,这些观察结果反映在人类癌症衍生数据中,将ASNS过度表达与多种癌症的不良临床结果联系起来。
总之,该数据记录了通过自噬和ASNS调控的广泛但特异性的天冬酰胺稳态,突出了先前未被认识的自噬在恶性KRAS驱动的肿瘤进展中的作用。

原始出处:
H. Helen Lin et al. Autophagic Reliance Promotes Metabolic Reprogramming in Oncogenic KRAS-driven Tumorigenesis. AUTOPHAGY 2018, DOI: https://doi.org/10.1080/15548627.2018.1450708

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    2018-07-04 sunfeifeiyang

    学习

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    2018-07-04 神功盖世

    学习

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    2018-07-04 jihuaijun1112

    学习学习学习

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createdName=zb1235672, createdTime=Tue Jul 03 07:18:30 CST 2018, time=2018-07-03, status=1, ipAttribution=)]
    2018-07-03 神功盖世

    0

  5. 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    2018-07-03 apple57298871

    0

  6. 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    2018-07-03 衣带渐宽

    学习

    0

  7. 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createdBy=8bff2327056, createdName=kafei, createdTime=Tue Jul 03 07:37:12 CST 2018, time=2018-07-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=328905, encodeId=de9e3289052a, content=优质资源.共同学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=19, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/oLAjfB7s1ib06iaV3D9Tg5K0LqDY57Aia0TOQByoJhNt3icm4sfukp500hLH6RHOpFdV01NbECtAV7s0qKpQPibyRukQAwAmqJU3X/0, createdBy=f91f1928792, createdName=九九消寒, createdTime=Tue Jul 03 07:27:46 CST 2018, time=2018-07-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=328891, encodeId=22163288917a, content=学习了!!!!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=59321624668, createdName=zb1235672, createdTime=Tue Jul 03 07:18:30 CST 2018, time=2018-07-03, status=1, ipAttribution=)]
    2018-07-03 龙胆草

    学习谢谢分享

    0

  8. 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time=2018-07-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=328916, encodeId=536c3289168f, content=学习谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4Nd44v3xHnnictn9UpctwtH62EPQ59TMdI9lnqHMgQ16nH7GmGCfpzicsHgjibYVk6vwSpXrC86gMibRkoaIzf5HwSz7/0, createdBy=78cc1691107, createdName=龙胆草, createdTime=Tue Jul 03 08:08:35 CST 2018, time=2018-07-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=328909, encodeId=c05932890956, content=学习了谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLbTp9nZtjwVrSZNxAXbAicnKQWnic2eBdJUQYhxO36XdkstSicr7FVF8p5ReH4omtmsbnLdvZLiaJJ1A/132, 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createdName=zb1235672, createdTime=Tue Jul 03 07:18:30 CST 2018, time=2018-07-03, status=1, ipAttribution=)]
    2018-07-03 kafei

    学习了谢谢

    0

  9. 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createdName=zb1235672, createdTime=Tue Jul 03 07:18:30 CST 2018, time=2018-07-03, status=1, ipAttribution=)]
    2018-07-03 九九消寒

    优质资源.共同学习

    0

  10. 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createdName=zb1235672, createdTime=Tue Jul 03 07:18:30 CST 2018, time=2018-07-03, status=1, ipAttribution=)]
    2018-07-03 zb1235672

    学习了!!!!!

    0

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活性氧(ROS)产生是糖尿病β细胞功能障碍的关键因素。既往研究表明,多效性的细胞因子IL-6与β细胞自噬相关,但IL-6是否影响β细胞的氧化应激尚不明确。Michelle R. Marasco等人利用糖尿病小鼠模型、体外培养的人类胰岛和啮齿动物的β细胞来研究IL-6是否影响氧化应激反应。结果显示IL-6偶联自噬抗氧化应激,可减少β细胞和人类胰岛的ROS。在活体内,β细胞特异性丧失IL-6信号使小鼠

J Periodontol: 牙周膜间充质干细胞自噬激活促进牙周炎血管生成

牙齿支持组织中的血管生成改变在牙周炎中起重要作用。间充质干细胞(MSC)可以通过旁分泌功能影响内皮细胞(EC)的血管形成。据报道,自噬与细胞分泌密切相关。

AUTOPHAGY:自噬缺陷诱导骨流失

在最近的一项研究中,来自西安交通大学的研究人员使用成骨细胞特异性Atg7(自噬相关7)条件性敲除(cKO)小鼠研究了ATG7在体内发育和重塑阶段的直接作用。