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Nat Commun:癌细胞是“聪明的小混蛋”:脂肪代谢反而使其扩散加快

2017-03-20 佚名 来宝网

肝癌是全世界癌症相关死亡的第三大原因,是澳大利亚增长最快的癌症。来自UNSW的副教授Kyle Hoehn说:“许多人怀疑肝癌的致命性在于细胞代谢过程。人们认为这种脂肪生产在帮助癌细胞增殖中发挥重要作用”。由Hoehn领导的团队设法成功阻止转基因小鼠的肝细胞中的脂肪生成,存在意想不到的后果。不像团队预测的那样终止了癌细胞的生长,阻断这种代谢途径导致两倍多的肿瘤的出现。令人惊讶的结果在本周发表在Nat


肝癌是全世界癌症相关死亡的第三大原因,是澳大利亚增长最快的癌症。

来自UNSW的副教授Kyle Hoehn说:“许多人怀疑肝癌的致命性在于细胞代谢过程。人们认为这种脂肪生产在帮助癌细胞增殖中发挥重要作用”。

由Hoehn领导的团队设法成功阻止转基因小鼠的肝细胞中的脂肪生成,存在意想不到的后果。

不像团队预测的那样终止了癌细胞的生长,阻断这种代谢途径导致两倍多的肿瘤的出现。令人惊讶的结果在本周发表在Nature Communications上。

Hoehn说,目前正在开发药物来靶向和阻断这种代谢途径,这被认为有希望治疗肝脏和其他癌症。他说这些结果可能引起一些关注,至少对于肝癌。

“我们的发现是完全违反直觉的,但它清楚地表明,任何使用这些药物治疗肝癌的,应在未来更谨慎,因为可能会有意想不到的后果。

当细胞分裂时,它们需要重建其所有的结构组分,包括其由脂肪制成的保护膜,并且通过脂质生成促进该过程。

Hoehn说:“脂肪生成是侵袭性肝癌的标志,高脂肪生成肿瘤患者的生存率最低”。

“在我们开始这个实验之前,我们相信,如果你可以敲除脂肪生成的腿,那么你可以阻止癌细胞如此迅速的形成或增殖。

该团队测试了他们的基因修饰小鼠是否可以通过暴露于DNA损伤的致癌物质并引入高脂肪饮食来获得癌症。这些损伤增加了生命晚期肿瘤发展的风险。

在9个月大时,他们比较了基因修饰的小鼠和具有正常肝脂肪生成的小鼠的肿瘤负荷。

“结果非常令人惊讶,”Hoehn说。

此外,研究小组发现癌细胞迅速适应脂肪生成的丧失:它们开始从血液中清除更多的脂肪,并通过燃烧更少的脂肪来更有效地保存这种脂肪。因此,通过踢出一条腿的脂质代谢,越来越强。

“癌细胞似乎总有解决方法,”Hoehn说:“他们是聪明的小混蛋”。

虽然在表面上看起来像癌症治疗的一个倒退,Hoehn说这个发现已经揭示了对癌细胞的复杂生物学的有价值的洞察,并且还确定了未来药物的可能的新靶标:驱动抗氧化防御系统的机制或脂肪摄取。

原始出处:

Nelson ME, Lahiri S, Chow JD,et al.  Inhibition of hepatic lipogenesis enhances liver tumorigenesis by increasing antioxidant defence and promoting cell survival.  Nat Commun. 2017 Mar 14.

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    2017-08-18 liye789132251
  2. [GetPortalCommentsPageByObjectIdResponse(id=1881768, encodeId=38451881e684b, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Fri Aug 18 18:54:00 CST 2017, time=2017-08-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2086961, encodeId=8c152086961fb, content=<a href='/topic/show?id=490750196b' target=_blank style='color:#2F92EE;'>#COMMUN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5019, encryptionId=490750196b, topicName=COMMUN)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7931272, createdName=liuli5079, createdTime=Fri May 05 23:54:00 CST 2017, time=2017-05-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1252205, encodeId=e323125220524, 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=91, 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 Mar 22 11:54:00 CST 2017, time=2017-03-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1620834, encodeId=81bc162083458, content=<a href='/topic/show?id=9d858084092' target=_blank style='color:#2F92EE;'>#聪明#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=80840, encryptionId=9d858084092, topicName=聪明)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=316420160942, createdName=Boyinsh, createdTime=Wed Mar 22 11:54:00 CST 2017, time=2017-03-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1628756, encodeId=71db1628e564c, content=<a href='/topic/show?id=02bd84324c4' target=_blank style='color:#2F92EE;'>#脂肪代谢#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84324, encryptionId=02bd84324c4, topicName=脂肪代谢)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d77721191523, createdName=zhangph, createdTime=Wed Mar 22 11:54:00 CST 2017, time=2017-03-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=181630, encodeId=9f92181630f8, content=这个发现已经揭示了对癌细胞的复杂生物学的有价值的洞察,并且还确定了未来药物的可能的新靶标:驱动抗氧化防御系统的机制或脂肪摄取。, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7s7ZCKOmmbBTD6nE7gcd5OZpvyGEzkxBP3S275k5ZJVrsPkotZhBglRHM9rKvcj1OgkssqhcnoPw8zIaMZTF8c/0, createdBy=4c441942088, createdName=ylzr123, createdTime=Tue Mar 21 09:16:30 CST 2017, time=2017-03-21, status=1, ipAttribution=)]
    2017-05-05 liuli5079
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    2017-03-22 yxch36
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    2017-03-22 Boyinsh
  5. [GetPortalCommentsPageByObjectIdResponse(id=1881768, encodeId=38451881e684b, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Fri Aug 18 18:54:00 CST 2017, time=2017-08-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2086961, encodeId=8c152086961fb, content=<a href='/topic/show?id=490750196b' target=_blank style='color:#2F92EE;'>#COMMUN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5019, encryptionId=490750196b, topicName=COMMUN)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7931272, createdName=liuli5079, createdTime=Fri May 05 23:54:00 CST 2017, time=2017-05-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1252205, encodeId=e323125220524, 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=91, 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 Mar 22 11:54:00 CST 2017, time=2017-03-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1620834, encodeId=81bc162083458, content=<a href='/topic/show?id=9d858084092' target=_blank style='color:#2F92EE;'>#聪明#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=80840, encryptionId=9d858084092, topicName=聪明)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=316420160942, createdName=Boyinsh, createdTime=Wed Mar 22 11:54:00 CST 2017, time=2017-03-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1628756, encodeId=71db1628e564c, content=<a href='/topic/show?id=02bd84324c4' target=_blank style='color:#2F92EE;'>#脂肪代谢#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84324, encryptionId=02bd84324c4, topicName=脂肪代谢)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d77721191523, createdName=zhangph, createdTime=Wed Mar 22 11:54:00 CST 2017, time=2017-03-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=181630, encodeId=9f92181630f8, content=这个发现已经揭示了对癌细胞的复杂生物学的有价值的洞察,并且还确定了未来药物的可能的新靶标:驱动抗氧化防御系统的机制或脂肪摄取。, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7s7ZCKOmmbBTD6nE7gcd5OZpvyGEzkxBP3S275k5ZJVrsPkotZhBglRHM9rKvcj1OgkssqhcnoPw8zIaMZTF8c/0, createdBy=4c441942088, createdName=ylzr123, createdTime=Tue Mar 21 09:16:30 CST 2017, time=2017-03-21, status=1, ipAttribution=)]
  6. [GetPortalCommentsPageByObjectIdResponse(id=1881768, encodeId=38451881e684b, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Fri Aug 18 18:54:00 CST 2017, time=2017-08-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2086961, encodeId=8c152086961fb, content=<a href='/topic/show?id=490750196b' target=_blank style='color:#2F92EE;'>#COMMUN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5019, encryptionId=490750196b, topicName=COMMUN)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7931272, createdName=liuli5079, createdTime=Fri May 05 23:54:00 CST 2017, time=2017-05-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1252205, encodeId=e323125220524, 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=91, 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 Mar 22 11:54:00 CST 2017, time=2017-03-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1620834, encodeId=81bc162083458, content=<a href='/topic/show?id=9d858084092' target=_blank style='color:#2F92EE;'>#聪明#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=80840, encryptionId=9d858084092, topicName=聪明)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=316420160942, createdName=Boyinsh, createdTime=Wed Mar 22 11:54:00 CST 2017, time=2017-03-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1628756, encodeId=71db1628e564c, content=<a href='/topic/show?id=02bd84324c4' target=_blank style='color:#2F92EE;'>#脂肪代谢#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84324, encryptionId=02bd84324c4, topicName=脂肪代谢)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d77721191523, createdName=zhangph, createdTime=Wed Mar 22 11:54:00 CST 2017, time=2017-03-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=181630, encodeId=9f92181630f8, content=这个发现已经揭示了对癌细胞的复杂生物学的有价值的洞察,并且还确定了未来药物的可能的新靶标:驱动抗氧化防御系统的机制或脂肪摄取。, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7s7ZCKOmmbBTD6nE7gcd5OZpvyGEzkxBP3S275k5ZJVrsPkotZhBglRHM9rKvcj1OgkssqhcnoPw8zIaMZTF8c/0, createdBy=4c441942088, createdName=ylzr123, createdTime=Tue Mar 21 09:16:30 CST 2017, time=2017-03-21, status=1, ipAttribution=)]
    2017-03-21 ylzr123

    这个发现已经揭示了对癌细胞的复杂生物学的有价值的洞察,并且还确定了未来药物的可能的新靶标:驱动抗氧化防御系统的机制或脂肪摄取。

    0

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