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Autophagy：ALDH1A1和HLTF调节溶酶体自噬抑制剂活性的作用在哪些癌症中具有较好的效果？

2017-10-13 fengxiangxin MedSci原创

溶酶体自噬抑制剂羟氯喹癌症ALDH1A1HLTF
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溶酶体自噬抑制剂（LAI）如羟氯喹（HCQ）在癌细胞系的一个子集中具有显著的活性。在癌症临床试验中已对 LAI 进行了评估，但对 LAI 敏感的遗传决定因素是未知的，因此难以预测哪种肿瘤最易受到影响。

溶酶体自噬抑制剂（LAI）如羟氯喹（HCQ）在癌细胞系的一个子集中具有显著的活性。在癌症临床试验中已对 LAI 进行了评估，但对 LAI 敏感的遗传决定因素是未知的，因此难以预测哪种肿瘤最易受到影响。

本研究为了进一步从基因水平了解 HCQ，研究者分别描述了对HCQ敏感（-S）和抵抗（-R）的癌细胞中的差异表达基因。值得注意的是，研究中发现典型的巨自噬/自噬（macroautophagy / autophagy）基因的表达与 HCQ 的敏感性无关。

通过ALDH1A1（醛脱氢酶1家族成员A1）和HLTF（解旋酶样转录因子）的表达模式研究者鉴定出了HCQ-S（ALDH1A1高表达HLTF低表达； ALDH1A1l低表达HLTF低表达）和HCQ-R（ALDH1A1低表达 HLTF高表达）细胞，并发现，ALDH1A1过表达时，在不会直接影响溶酶体功能或自噬通量的情况下能够增强 LAI 进入细胞以及增加细胞毒性。

HLTF 的表达允许修复由LAI诱导的活性氧引起的DNA损伤，并因此导致癌细胞对 HCQ 抵抗。在通过启动子甲基化沉默 HLTF 后，细胞对 HCQ 的敏感性增加。 HLTF的过表达使得氯喹衍生物在体外和体内的抗肿瘤功效均减弱。

通过对来自癌症和肿瘤基因图谱(Cancer Genome Atlas，TCGA)计划大于700例患者的RNA测序数据分析：研究者发现结肠癌，肾细胞癌和胃癌具有丰富的HCQ-S或HCQ-R特征。 这些结果为LAI疗效提供了机制性的见解，并为LAI的临床研究提供了指导。

原始出处：

Piao S， Ojha R， Rebecca VW.et al. ALDH1A1 and HLTF modulate the activity of lysosomal autophagy inhibitors in cancer cells. Autophagy. 2017 Oct 5：1-16. doi： 10.1080/15548627.2017.1377377.

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    2017-12-02 zgwhgch

    #ALDH1A1#

    0

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    2018-05-25 jklm09

    #抑制剂#

    0

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    2018-03-17 doctor-chen9595

    #溶酶体自噬抑制剂#

    0

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    2017-10-22 虈亣靌

    不错的.学习了!谢谢分享!

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=1779661, encodeId=1fb71e7966148, content=<a href='/topic/show?id=f9a222e9ca' target=_blank style='color:#2F92EE;'>#ALDH1A1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2279, encryptionId=f9a222e9ca, topicName=ALDH1A1)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=10ba218, createdName=zgwhgch, createdTime=Sat Dec 02 14:50:00 CST 2017, time=2017-12-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1851543, encodeId=395f1851543bf, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Fri May 25 20:50:00 CST 2018, time=2018-05-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1775898, encodeId=42001e758988d, content=<a href='/topic/show?id=c8a766525e8' target=_blank style='color:#2F92EE;'>#溶酶体自噬抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66525, encryptionId=c8a766525e8, topicName=溶酶体自噬抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=46df38838045, createdName=doctor-chen9595, createdTime=Sat Mar 17 20:50:00 CST 2018, time=2018-03-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=255142, encodeId=6c8d25514246, content=不错的.学习了!谢谢分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, 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=Sun Oct 22 19:12:52 CST 2017, time=2017-10-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=254284, encodeId=3d14254284b5, content=非常好.学习了.很受益, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, 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=Thu Oct 19 11:37:15 CST 2017, time=2017-10-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=253861, encodeId=5b332538610c, content=谢谢分享.很好, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a6831717982, createdName=微分, createdTime=Tue Oct 17 23:27:37 CST 2017, time=2017-10-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=253345, encodeId=2f92253345e9, content=很好很好很好, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/10/07/8c1e5a0085f3b74f3a4ab58a38a3d487.jpg, createdBy=b33e2159612, createdName=2227437833_79976374, createdTime=Mon Oct 16 08:16:20 CST 2017, time=2017-10-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1469399, encodeId=11081469399c1, content=<a href='/topic/show?id=9d6522e613' target=_blank style='color:#2F92EE;'>#ALD#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2276, encryptionId=9d6522e613, topicName=ALD)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=64f67025397, createdName=zhangjingnwpu, createdTime=Sun Oct 15 07:50:00 CST 2017, time=2017-10-15, status=1, ipAttribution=)]
    2017-10-19 虈亣靌

    非常好.学习了.很受益

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1779661, encodeId=1fb71e7966148, content=<a href='/topic/show?id=f9a222e9ca' target=_blank style='color:#2F92EE;'>#ALDH1A1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2279, encryptionId=f9a222e9ca, topicName=ALDH1A1)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=10ba218, createdName=zgwhgch, createdTime=Sat Dec 02 14:50:00 CST 2017, time=2017-12-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1851543, encodeId=395f1851543bf, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Fri May 25 20:50:00 CST 2018, time=2018-05-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1775898, encodeId=42001e758988d, content=<a href='/topic/show?id=c8a766525e8' target=_blank style='color:#2F92EE;'>#溶酶体自噬抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66525, encryptionId=c8a766525e8, topicName=溶酶体自噬抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=46df38838045, createdName=doctor-chen9595, createdTime=Sat Mar 17 20:50:00 CST 2018, time=2018-03-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=255142, encodeId=6c8d25514246, content=不错的.学习了!谢谢分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, 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=Sun Oct 22 19:12:52 CST 2017, time=2017-10-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=254284, encodeId=3d14254284b5, content=非常好.学习了.很受益, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, 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=Thu Oct 19 11:37:15 CST 2017, time=2017-10-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=253861, encodeId=5b332538610c, content=谢谢分享.很好, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a6831717982, createdName=微分, createdTime=Tue Oct 17 23:27:37 CST 2017, time=2017-10-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=253345, encodeId=2f92253345e9, content=很好很好很好, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/10/07/8c1e5a0085f3b74f3a4ab58a38a3d487.jpg, createdBy=b33e2159612, createdName=2227437833_79976374, createdTime=Mon Oct 16 08:16:20 CST 2017, time=2017-10-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1469399, encodeId=11081469399c1, content=<a href='/topic/show?id=9d6522e613' target=_blank style='color:#2F92EE;'>#ALD#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2276, encryptionId=9d6522e613, topicName=ALD)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=64f67025397, createdName=zhangjingnwpu, createdTime=Sun Oct 15 07:50:00 CST 2017, time=2017-10-15, status=1, ipAttribution=)]
    2017-10-17 微分

    谢谢分享.很好

    0

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    2017-10-16 2227437833_79976374

    很好很好很好

    0

  8. [GetPortalCommentsPageByObjectIdResponse(id=1779661, encodeId=1fb71e7966148, content=<a href='/topic/show?id=f9a222e9ca' target=_blank style='color:#2F92EE;'>#ALDH1A1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2279, encryptionId=f9a222e9ca, topicName=ALDH1A1)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=10ba218, createdName=zgwhgch, createdTime=Sat Dec 02 14:50:00 CST 2017, time=2017-12-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1851543, encodeId=395f1851543bf, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Fri May 25 20:50:00 CST 2018, time=2018-05-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1775898, encodeId=42001e758988d, content=<a href='/topic/show?id=c8a766525e8' target=_blank style='color:#2F92EE;'>#溶酶体自噬抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66525, encryptionId=c8a766525e8, topicName=溶酶体自噬抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=46df38838045, createdName=doctor-chen9595, createdTime=Sat Mar 17 20:50:00 CST 2018, time=2018-03-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=255142, encodeId=6c8d25514246, content=不错的.学习了!谢谢分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, 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=Sun Oct 22 19:12:52 CST 2017, time=2017-10-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=254284, encodeId=3d14254284b5, content=非常好.学习了.很受益, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, 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=Thu Oct 19 11:37:15 CST 2017, time=2017-10-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=253861, encodeId=5b332538610c, content=谢谢分享.很好, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a6831717982, createdName=微分, createdTime=Tue Oct 17 23:27:37 CST 2017, time=2017-10-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=253345, encodeId=2f92253345e9, content=很好很好很好, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/10/07/8c1e5a0085f3b74f3a4ab58a38a3d487.jpg, createdBy=b33e2159612, createdName=2227437833_79976374, createdTime=Mon Oct 16 08:16:20 CST 2017, time=2017-10-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1469399, encodeId=11081469399c1, content=<a href='/topic/show?id=9d6522e613' target=_blank style='color:#2F92EE;'>#ALD#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2276, encryptionId=9d6522e613, topicName=ALD)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=64f67025397, createdName=zhangjingnwpu, createdTime=Sun Oct 15 07:50:00 CST 2017, time=2017-10-15, status=1, ipAttribution=)]
    2017-10-15 zhangjingnwpu

    #ALD#

    0