Cell Death Dis:FXR通过拮抗Wnt/β-catenin信号发挥抑癌作用

2020-09-01 QQY MedSci原创

结直肠癌(CRC)作为癌症相关死亡的第二大主要原因,全球每年约有1,800,000例新病例被确诊为CRC。尽管目前在CRC的治疗上已取得了较大的进展,但由于晚期CRC患者的肿瘤远端转移和复发,该疾病的

结直肠癌(CRC)作为癌症相关死亡的第二大主要原因,全球每年约有1,800,000例新病例被确诊为CRC。尽管目前在CRC的治疗上已取得了较大的进展,但由于晚期CRC患者的肿瘤远端转移和复发,该疾病的预后仍不令人满意。越来越多的研究显示CRC的分子发病机制是一个多步骤且连续的过程,因此探究结直肠癌发生发展的精确机制对于制定更好治疗策略至关重要。

既往研究发现,胆汁酸广泛参与包括肝细胞癌、胃癌、食道癌和胰腺癌等人恶性肿瘤的发病机理。而粪便中的胆汁酸水平升高与结直肠癌的发生息息相关。FXR(法尼醇X受体,由NR1H4编码)作为胆汁酸的核受体,是胆汁酸稳态的关键调节因子,越来越多的证据显示在人肿瘤发生发展过程中FXR起着关键作用。然而在CRC中FXR所行使的功能和确切的分子机制仍有待进一步研究。

在这项研究中,研究人员旨在探究结直肠癌发生发展过程中FXR和Wnt/β-catenin信号转导通路之间的相关性。研究人员发现在结直肠癌组织中FXR的表达水平被下调,且与患者预后不良相关。体外抑制FXR的表达水平能够促进结直肠癌细胞的生长和侵袭能力,而内源抑制其表达则能够促进移植瘤的形成和远端转移,而FXR的异位表达则呈现相反的表型。

机制研究显示,FXR能够通过拮抗Wnt/β-catenin信号转导通路发挥其肿瘤抑制作用。此外研究人员证实了在结直肠癌细胞中的FXR/β-catenin的相互作用,该相互作用能够削弱β-catenin/TCF4复合物的形成。此外,研究人员还发现β-catenin缺失会增加FXR对SHP的转录激活作用。

总而言之,本研究结果显示在结直肠癌中,FXR能够通过拮抗Wnt/β-catenin信号转导通路发挥肿瘤抑制作用。

原始出处:
Yu, J., Li, S., Guo, J. et al. Farnesoid X receptor antagonizes Wnt/β-catenin signaling in colorectal tumorigenesis. Cell Death Dis 11, 640 (17 August 2020).

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topicName=肝细胞癌)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Wed Sep 02 18:28:08 CST 2020, time=2020-09-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=882162, encodeId=fe8288216268, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=efb05136804, createdName=14669b93m32暂无昵称, createdTime=Wed Sep 02 11:13:07 CST 2020, time=2020-09-02, status=1, ipAttribution=)]
    2020-09-25 金牛♉

    受益了

    0

  5. 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  6. 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topicName=肝细胞癌)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Wed Sep 02 18:28:08 CST 2020, time=2020-09-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=882162, encodeId=fe8288216268, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=efb05136804, createdName=14669b93m32暂无昵称, createdTime=Wed Sep 02 11:13:07 CST 2020, time=2020-09-02, status=1, ipAttribution=)]
    2020-09-03 cy0328
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topicName=肝细胞癌)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Wed Sep 02 18:28:08 CST 2020, time=2020-09-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=882162, encodeId=fe8288216268, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=efb05136804, createdName=14669b93m32暂无昵称, createdTime=Wed Sep 02 11:13:07 CST 2020, time=2020-09-02, status=1, ipAttribution=)]
    2020-09-03 zhwj
  8. 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topicName=肝细胞癌)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Wed Sep 02 18:28:08 CST 2020, time=2020-09-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=882162, encodeId=fe8288216268, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=efb05136804, createdName=14669b93m32暂无昵称, createdTime=Wed Sep 02 11:13:07 CST 2020, time=2020-09-02, status=1, ipAttribution=)]
    2020-09-03 爆笑小医
  9. 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content=<a href='/topic/show?id=b506e7489b' target=_blank style='color:#2F92EE;'>#FXR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7748, encryptionId=b506e7489b, topicName=FXR)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=395f25, createdName=爆笑小医, createdTime=Thu Sep 03 13:30:43 CST 2020, time=2020-09-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=882239, encodeId=ad3888223906, content=<a href='/topic/show?id=24448348527' target=_blank style='color:#2F92EE;'>#胆汁酸#</a>广泛参与包括<a href='/topic/show?id=735a81364b7' target=_blank style='color:#2F92EE;'>#肝细胞癌#</a>、胃癌、食道癌和胰腺癌等人恶性肿瘤的发病机理, beContent=null, objectType=article, channel=null, level=null, likeNumber=249, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83485, encryptionId=24448348527, topicName=胆汁酸), TopicDto(id=81364, encryptionId=735a81364b7, topicName=肝细胞癌)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Wed Sep 02 18:28:08 CST 2020, time=2020-09-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=882162, encodeId=fe8288216268, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=efb05136804, createdName=14669b93m32暂无昵称, createdTime=Wed Sep 02 11:13:07 CST 2020, time=2020-09-02, status=1, ipAttribution=)]
    2020-09-02 lovetcm

    #胆汁酸#广泛参与包括#肝细胞癌#、胃癌、食道癌和胰腺癌等人恶性肿瘤的发病机理

    0

  10. 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topicName=肝细胞癌)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Wed Sep 02 18:28:08 CST 2020, time=2020-09-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=882162, encodeId=fe8288216268, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=efb05136804, createdName=14669b93m32暂无昵称, createdTime=Wed Sep 02 11:13:07 CST 2020, time=2020-09-02, status=1, ipAttribution=)]
    2020-09-02 14669b93m32暂无昵称

    学习

    0

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这例37岁女性两度被诊断“肠癌”,但找不到肿瘤细胞!结局却峰回路转...

37岁青年女性病情迁延2年,腹痛、包块、便血、肠腔高度狭窄、肿瘤标志物升高……两度入院均考虑“肠癌”,然而两次肠镜活检都未及肿瘤细胞,最终真相揭晓,让她又“喜”,又“惊”!

JAMA Oncology:结直肠癌同期孤立腹膜转移早期切除术后全身辅助化疗与积极监测的疗效比较

据统计,在全世界约430个治疗中心中,约有四分之一的结直肠癌同期孤立腹膜转移患者接受了细胞减灭术和腹腔热灌注化疗。一个国际上存在争议的话题是结直肠癌同期孤立腹膜转移患者是否应该接受全身辅助化疗。

CELL:颠覆传统观念,染色质拓扑变化可抑制结直肠癌的恶性进展

最近,研究人员在CELL杂志发文,将结肠肿瘤和正常结肠的拓扑图与表观遗传学、转录和成像数据整合在一起,以表征染色质环、拓扑相关域和大规模隔室的改变。

Molecular Cancer:外泌体促进结直肠癌的进展

结直肠癌(Colorectal cancer, CRC)是全球最常见的恶性肿瘤之一,转移和复发的风险极高。考虑到传统疗法的缺点,如毒性和耐受不良,临床结果仍然不能令人满意。

警惕!夜间暴露于蓝光会增加结直肠癌的风险!

先前有研究发现,夜间暴露于人造光(尤其是蓝光)与各种不良健康影响之间存在关联,包括睡眠障碍、肥胖症和各种类型的癌症风险增加,尤其是在夜班工人中。蓝光是大多数白色LED以及许多平板电脑和手机屏幕发出的可

Nat Commun:哪些局部晚期直肠癌患者才能从化疗中获益?

辅助化疗只能降低DM的风险,并只在某些亚组患者中提供额外的生存获益,还有一些患者在治疗后甚至可能获得更糟糕的结果。因此,如何检测出可以从辅助化疗中获益的LARC患者至关重要。