Autophagy:卵巢癌细胞是怎么被杀死的?

2018-01-29 海北 MedSci原创

在DIRAS家族的3个GTP酶中,DIRAS3 / ARHI已经被研究人员进行了较为详细的探究。DIRAS3是一个印迹肿瘤抑制基因,编码一个26-kDa的与RAS和RAP具有60%同源性的GTP酶。

DIRAS家族的3GTP酶中DIRAS3 / ARHI已经被研究人员进行了较为详细的探究DIRAS3是一个印迹肿瘤抑制基因编码一个26-kDa的与RASRAP具有60同源性的GTPDIRAS3在包括卵巢癌在内的许多肿瘤中都有所下调而且其重新表达能够抑制癌细胞的生长降低其运动性促进肿瘤休眠并诱导巨自噬/自噬

已有的研究证明DIRAS3是人类细胞自噬所必需的在进化重新排列期间Diras3已经从小鼠基因组中丢失但是小鼠细胞仍然可以进行自噬今日来自德克萨斯大学的研究人员探究了人和小鼠细胞中都存在的同系物DIRAS1DIRAS2是否可以作为小鼠基因组中的DIRAS3的替代物影响自噬和癌细胞生长

DIRAS3相似2GTP酶也与RASRAP具有40-50的同源性但是其与DIRAS3的主要不同之处在于其N-末端延伸的长度研究人员发现DIRAS1DIRAS2在卵巢癌细胞中有所下调并与无疾病和总生存期降低有关这些基因的重新表达可以通过诱导自噬介导的细胞死亡来抑制人和鼠卵巢癌细胞的生长

机制上说DIRAS1DIRAS2通过抑制AKT1-MTORRAS-MAPK信号通路并调节自噬相关转录因子FOXO3 / FOXO3ATFEB的核定位来诱导和调节自噬

综上所述这些数据表明DIRAS1DIRAS2可能作为DIRAS3的小鼠基因组的替代物并且可以充当微调人类自噬的备份系统

 

原始出处:

Margie N. Sutton et al. RAS-related GTPases DIRAS1 and DIRAS2 induce autophagic cancer cell death and are required for autophagy in murine ovarian cancer cellsAutophagy, 2018; DOI: https://doi.org/10.1080/15548627.2018.1427022

 

本文系梅斯医学(MedSci)原创编译整理,转载需授!

 


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    2018-01-31 yxch36
  3. [GetPortalCommentsPageByObjectIdResponse(id=1755467, encodeId=84f31e55467a7, content=<a href='/topic/show?id=459f368e114' target=_blank style='color:#2F92EE;'>#卵巢癌细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=36871, encryptionId=459f368e114, topicName=卵巢癌细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9f9536903522, createdName=qblt, createdTime=Sat Feb 10 22:50:00 CST 2018, time=2018-02-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1252456, encodeId=b227125245664, content=<a href='/topic/show?id=3efee1519b2' target=_blank style='color:#2F92EE;'>#癌细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=71519, encryptionId=3efee1519b2, topicName=癌细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4cea26, createdName=yxch36, createdTime=Wed Jan 31 12:50:00 CST 2018, time=2018-01-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=283330, encodeId=2dc528333032, content=学习一下学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3zSn0GqHrsfLGSUSR8zwnWWLT4FMl5XH8S58HuZslVkLsAPbXDXaliagK7TOxQfmngKibG1yrDonepCLDkcxGk8hS/0, createdBy=b8282062892, createdName=changjiu, createdTime=Mon Jan 29 23:00:54 CST 2018, time=2018-01-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=283322, encodeId=65472833222b, content=不错的文章值得拥有, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=eff51996281, createdName=1e1b8538m79(暂无匿称), createdTime=Mon Jan 29 22:53:37 CST 2018, time=2018-01-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=283312, encodeId=9887283312ee, content=不错的文章值得推荐, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=04f22055142, createdName=131****2916, createdTime=Mon Jan 29 22:22:52 CST 2018, time=2018-01-29, status=1, ipAttribution=)]
    2018-01-29 changjiu

    学习一下学习

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    2018-01-29 1e1b8538m79(暂无匿称)

    不错的文章值得拥有

    0

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    2018-01-29 131****2916

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