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Nature子刊:30%结直肠癌细胞的“命门”竟是一个氨基酸

2016-07-26 佚名 不详

结直肠癌是中国最常见的癌症类型之一,每年有超过300万的新增病例,且发病人群在近年来呈现出年轻化的趋势,成为了一个需要重点应对的公共健康问题。

最近,来自凯斯西储大学、第三军医大学等中美两国研究机构的科学家们发现,相当一部分的结肠癌对谷氨酰胺(glutamine)有着特殊的“嗜好”,对这一种非必需氨基酸有着高于其他细胞的需求。然而,嗜好往往会成为一个人的弱点乃至“命门”,对于癌细胞也同样如此。研究者认为,癌细胞的这一弱点可能成为下一个治疗结直肠癌的有效药物靶点。这一成果发表于近期的Nature子刊《Nature Communications》上。

▲谷氨酰胺结构

原来,这类对谷氨酰胺有着特殊嗜好的结肠癌细胞均带有PIK3CA基因突变,后者广泛存在多种类型的肿瘤中,包括约30%结肠癌细胞。该基因编码磷脂酰肌醇3-激酶(P13K)的催化亚基p110α。P13K对于细胞的增殖、存活和转移均具有重要的调控作用,其一旦被活化则可激活PI3K-Akt等经典信号通路,对细胞产生广泛的影响。这种突变的p110α会最终导致谷丙转氨酶2(GPT2)表达量的明显提高,而谷氨酰胺正是GPT2的底物。

▲三羧酸循环示意图

其实,谷氨酰胺对于癌细胞有着非同寻常的意义。不同于正常细胞,被癌细胞摄取的葡萄糖主要通过糖酵解途径分解为乳酸从而产生能量,即便是在有氧的情况下。另一方面,谷氨酰胺往往是癌细胞中三羧酸(TCA)循环的起点,其需通过包括谷丙转氨酶(GPT)在内的三种酶被转化为α-酮戊二酸(αKG),然后再正式进入TCA循环。在带有PIK3CA基因突变的癌细胞中,由于GPT2活性异常升高,使得对谷氨酰胺的需求量也大大提高,成为了这些癌细胞的“命门”。

当研究者停止向体外培养的携带PIK3CA基因突变的癌细胞供应谷氨酰胺时,这些癌细胞便会经不住“考验”而死亡,而不带有该突变的癌细胞则不受影响。不仅如此,当研究者向带有PIK3CA基因突变的结直肠癌小鼠模型注射氨基氧乙酸(aminooxyacetate)后,其肿瘤成长则会被抑制。氨基氧乙酸是包括GPT2在内多种转氨酶的小分子抑制剂。

▲氨基氧乙酸结构

“我们将基于这一发现于今年夏天在塞德曼癌症中心(University Hospitals Seidman Cancer Center)启动结直肠癌的临床试验,”文章作者之一、塞德曼癌症中心的Neal Meropol教授表示。在这一由他领导的临床试验中,研究者将测试某种谷氨酸代谢抑制剂对于晚期结直肠癌患者的治疗效果。(生物谷Bioon.com)

参考资料:

[1] Oncogenic PIK3CA mutations reprogram glutamine metabolism in colorectal cancer

[2] Case Western Reserve University researchers block common colon cancer tumor type in mice

[3] 全国肿瘤防治宣传周央视报道

相关会议推荐

2016(第八届)干细胞技术与临床转化论坛

会议时间:2016.10.14-2016.10.15     会议地点:北京

会议详情: http://www.bioon.com/z/2016stemcell/

同期活动:10月13日 iPSCs十年-技术、应用与未来愿景探讨高端沙龙:

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    2016-11-04 仁心济世
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    2016-07-28 yxch36
  5. [GetPortalCommentsPageByObjectIdResponse(id=1860824, encodeId=c90d186082495, content=<a href='/topic/show?id=5e746403ed5' target=_blank style='color:#2F92EE;'>#氨基酸#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64037, encryptionId=5e746403ed5, topicName=氨基酸)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=bf3d82, createdName=zhaohui6731, createdTime=Fri Dec 16 08:57:00 CST 2016, time=2016-12-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1805754, encodeId=c5e91805e54b5, content=<a href='/topic/show?id=95e7e87031b' target=_blank style='color:#2F92EE;'>#结直肠癌细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=112, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=78703, encryptionId=95e7e87031b, topicName=结直肠癌细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b78f2500065, createdName=12498761m56暂无昵称, createdTime=Mon Sep 05 07:57:00 CST 2016, time=2016-09-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1881214, encodeId=cace188121479, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=仁心济世, createdTime=Fri Nov 04 03:57:00 CST 2016, time=2016-11-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1252112, encodeId=16d2125211292, 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=65, 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=Thu Jul 28 08:57:00 CST 2016, time=2016-07-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1452813, encodeId=840514528139b, content=<a href='/topic/show?id=098ee8679ad' target=_blank style='color:#2F92EE;'>#结直肠#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=78679, encryptionId=098ee8679ad, topicName=结直肠)], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=9ace5575596, createdName=crystal0564, createdTime=Thu Jul 28 08:57:00 CST 2016, time=2016-07-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=94848, encodeId=640394848dc, content=有突破就很好, beContent=null, objectType=article, channel=null, level=null, likeNumber=109, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfdY7yem1P7bRvOP6z0jKsBoYR8ezfAricY7meQWcte7LRJsWHVn0CnPJg2JuQmevR0DoFmmEib5QLD2kNESBESQT/0, createdBy=59191706502, createdName=医路开来, createdTime=Wed Jul 27 11:14:00 CST 2016, time=2016-07-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=94778, encodeId=363494e7878, content=继续关注!, beContent=null, objectType=article, channel=null, level=null, likeNumber=143, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=93f31631454, createdName=1dd8c52fm63(暂无匿称), createdTime=Tue Jul 26 22:02:00 CST 2016, time=2016-07-26, status=1, ipAttribution=)]
  6. [GetPortalCommentsPageByObjectIdResponse(id=1860824, encodeId=c90d186082495, content=<a href='/topic/show?id=5e746403ed5' target=_blank style='color:#2F92EE;'>#氨基酸#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64037, encryptionId=5e746403ed5, topicName=氨基酸)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=bf3d82, createdName=zhaohui6731, createdTime=Fri Dec 16 08:57:00 CST 2016, time=2016-12-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1805754, encodeId=c5e91805e54b5, content=<a href='/topic/show?id=95e7e87031b' target=_blank style='color:#2F92EE;'>#结直肠癌细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=112, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=78703, encryptionId=95e7e87031b, topicName=结直肠癌细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b78f2500065, createdName=12498761m56暂无昵称, createdTime=Mon Sep 05 07:57:00 CST 2016, time=2016-09-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1881214, encodeId=cace188121479, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=仁心济世, createdTime=Fri Nov 04 03:57:00 CST 2016, time=2016-11-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1252112, encodeId=16d2125211292, 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=65, 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=Thu Jul 28 08:57:00 CST 2016, time=2016-07-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1452813, encodeId=840514528139b, content=<a href='/topic/show?id=098ee8679ad' target=_blank style='color:#2F92EE;'>#结直肠#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=78679, encryptionId=098ee8679ad, topicName=结直肠)], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=9ace5575596, createdName=crystal0564, createdTime=Thu Jul 28 08:57:00 CST 2016, time=2016-07-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=94848, encodeId=640394848dc, content=有突破就很好, beContent=null, objectType=article, channel=null, level=null, likeNumber=109, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfdY7yem1P7bRvOP6z0jKsBoYR8ezfAricY7meQWcte7LRJsWHVn0CnPJg2JuQmevR0DoFmmEib5QLD2kNESBESQT/0, createdBy=59191706502, createdName=医路开来, createdTime=Wed Jul 27 11:14:00 CST 2016, time=2016-07-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=94778, encodeId=363494e7878, content=继续关注!, beContent=null, objectType=article, channel=null, level=null, likeNumber=143, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=93f31631454, createdName=1dd8c52fm63(暂无匿称), createdTime=Tue Jul 26 22:02:00 CST 2016, time=2016-07-26, status=1, ipAttribution=)]
    2016-07-27 医路开来

    有突破就很好

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=1860824, encodeId=c90d186082495, content=<a href='/topic/show?id=5e746403ed5' target=_blank style='color:#2F92EE;'>#氨基酸#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64037, encryptionId=5e746403ed5, topicName=氨基酸)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=bf3d82, createdName=zhaohui6731, createdTime=Fri Dec 16 08:57:00 CST 2016, time=2016-12-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1805754, encodeId=c5e91805e54b5, content=<a href='/topic/show?id=95e7e87031b' target=_blank style='color:#2F92EE;'>#结直肠癌细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=112, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=78703, encryptionId=95e7e87031b, topicName=结直肠癌细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b78f2500065, createdName=12498761m56暂无昵称, createdTime=Mon Sep 05 07:57:00 CST 2016, time=2016-09-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1881214, encodeId=cace188121479, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=仁心济世, createdTime=Fri Nov 04 03:57:00 CST 2016, time=2016-11-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1252112, encodeId=16d2125211292, 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=65, 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=Thu Jul 28 08:57:00 CST 2016, time=2016-07-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1452813, encodeId=840514528139b, content=<a href='/topic/show?id=098ee8679ad' target=_blank style='color:#2F92EE;'>#结直肠#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=78679, encryptionId=098ee8679ad, topicName=结直肠)], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=9ace5575596, createdName=crystal0564, createdTime=Thu Jul 28 08:57:00 CST 2016, time=2016-07-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=94848, encodeId=640394848dc, content=有突破就很好, beContent=null, objectType=article, channel=null, level=null, likeNumber=109, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfdY7yem1P7bRvOP6z0jKsBoYR8ezfAricY7meQWcte7LRJsWHVn0CnPJg2JuQmevR0DoFmmEib5QLD2kNESBESQT/0, createdBy=59191706502, createdName=医路开来, createdTime=Wed Jul 27 11:14:00 CST 2016, time=2016-07-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=94778, encodeId=363494e7878, content=继续关注!, beContent=null, objectType=article, channel=null, level=null, likeNumber=143, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=93f31631454, createdName=1dd8c52fm63(暂无匿称), createdTime=Tue Jul 26 22:02:00 CST 2016, time=2016-07-26, status=1, ipAttribution=)]
    2016-07-26 1dd8c52fm63(暂无匿称)

    继续关注!

    0

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