Cell Death Differ:TRIM28–RLIM–MDM2–p53通路影响肺癌的发生发展

2020-12-27 xiaozeng MedSci原创

肺癌是全球癌症死亡的主要原因之一, 目前已导致全球超过100万人死亡。由于该疾病具有较高的晚期诊断率和转移潜力,肺癌的5年生存率仅为15%。

肺癌是全球癌症死亡的主要原因之一, 目前已导致全球超过100万人死亡。由于该疾病具有较高的晚期诊断率和转移潜力,肺癌的5年生存率仅为15%。

诸如吉非替尼(gefitinib)和厄洛替尼(erlotinib)等靶向RTK(受体酪氨酸激酶)或EGFR(表皮生长因子受体)的抗癌药物已在患者中表现出了一定的疗效,但大多数的非小细胞肺癌(NSCLC)患者仍出现耐药性和肿瘤转移倾向。


TRIM28(也称为KAP1或TIF1-β)是一种具有多种细胞内调节功能的E3泛素连接酶,其作为核定位的辅抑制因子,其能够DNA损伤响应和维持干细胞的多能性等。既往研究显示,TRIM28可与MDM2协同调节骨肉瘤细胞中p53的泛素化和降解。

TRIM28在肺癌组织中的特性

在该研究中,研究人员旨在鉴定新的肺癌生物标记物,研究人员通过检测肺癌患者的肿瘤组织以及对应的非肿瘤组织中的蛋白质表达水平变化,发现TRIM28蛋白在肺癌组织中高表达。


进一步的研究显示,在肺癌细胞和移植瘤模型中,TRIM28的稳定过表达能够显著提高细胞增殖、迁移和侵袭能力,而敲低TRIM28则具有相反的作用。 此外,研究人员揭示了在肺癌中TRIM28起着致癌基因的功能,其能够通过靶向调节泛素连接酶RLIM和MDM2下调p53的表达水平。且TRIM28和RLIM的表达水平与患者的总体生存率相关。

相关模式图

总而言之,以上的研究结果阐明了TRIM28–RLIM–MDM2–p53这一级联的精确调控机制,该机制也为肺癌的发生发展提供了新见解,该通路或可成为该疾病潜在的治疗靶标。


原始出处:

Jin, JO., Lee, G.D., Nam, S.H. et al. Sequential ubiquitination of p53 by TRIM28, RLIM, and MDM2 in lung tumorigenesis. Cell Death Differ (16 December 2020).

 

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    2021-04-09 wangyang7970
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    2021-08-12 维他命
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    2021-09-22 jinweidong
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    2021-09-22 isabellayj
  6. [GetPortalCommentsPageByObjectIdResponse(id=1746670, encodeId=51de1e46670a1, content=<a href='/topic/show?id=8564114128c' target=_blank style='color:#2F92EE;'>#MDM2#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11412, encryptionId=8564114128c, topicName=MDM2)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=fba635824905, createdName=wangyang7970, createdTime=Fri Apr 09 17:23:57 CST 2021, time=2021-04-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1872105, encodeId=c6cb18e210556, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Tue Feb 23 03:23:57 CST 2021, time=2021-02-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1962407, encodeId=f689196240eea, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Thu Aug 12 02:23:57 CST 2021, time=2021-08-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2024632, encodeId=e513202463201, content=<a href='/topic/show?id=d0301e8225a' target=_blank style='color:#2F92EE;'>#Trim28#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17822, encryptionId=d0301e8225a, topicName=Trim28)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=dc7a157, createdName=jinweidong, createdTime=Wed Sep 22 02:23:57 CST 2021, time=2021-09-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1784239, encodeId=434e1e8423965, content=<a href='/topic/show?id=f01159527d' target=_blank style='color:#2F92EE;'>#Differ#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5952, encryptionId=f01159527d, topicName=Differ)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d784426, createdName=isabellayj, createdTime=Wed Sep 22 08:23:57 CST 2021, time=2021-09-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2030803, encodeId=5e36203080388, content=<a href='/topic/show?id=71353e8964f' target=_blank style='color:#2F92EE;'>#发生发展#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37896, encryptionId=71353e8964f, topicName=发生发展)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=346311, createdName=wgsun, createdTime=Sun Mar 21 17:23:57 CST 2021, time=2021-03-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1372438, encodeId=47e213e243866, content=<a href='/topic/show?id=9d861362e53' target=_blank style='color:#2F92EE;'>#p53#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13627, encryptionId=9d861362e53, topicName=p53)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5d70341, createdName=zhishijing, createdTime=Mon Dec 28 15:23:57 CST 2020, time=2020-12-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1531710, encodeId=fe311531e104e, content=<a href='/topic/show?id=770e5e9457' target=_blank style='color:#2F92EE;'>#Death#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5794, encryptionId=770e5e9457, topicName=Death)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=32e312278742, createdName=cy0328, createdTime=Mon Dec 28 15:23:57 CST 2020, time=2020-12-28, status=1, ipAttribution=)]
  7. [GetPortalCommentsPageByObjectIdResponse(id=1746670, encodeId=51de1e46670a1, content=<a href='/topic/show?id=8564114128c' target=_blank style='color:#2F92EE;'>#MDM2#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11412, encryptionId=8564114128c, topicName=MDM2)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=fba635824905, createdName=wangyang7970, createdTime=Fri Apr 09 17:23:57 CST 2021, time=2021-04-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1872105, encodeId=c6cb18e210556, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Tue Feb 23 03:23:57 CST 2021, time=2021-02-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1962407, encodeId=f689196240eea, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Thu Aug 12 02:23:57 CST 2021, time=2021-08-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2024632, encodeId=e513202463201, content=<a href='/topic/show?id=d0301e8225a' target=_blank style='color:#2F92EE;'>#Trim28#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17822, encryptionId=d0301e8225a, topicName=Trim28)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=dc7a157, createdName=jinweidong, createdTime=Wed Sep 22 02:23:57 CST 2021, time=2021-09-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1784239, encodeId=434e1e8423965, content=<a href='/topic/show?id=f01159527d' target=_blank style='color:#2F92EE;'>#Differ#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5952, encryptionId=f01159527d, topicName=Differ)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d784426, createdName=isabellayj, createdTime=Wed Sep 22 08:23:57 CST 2021, time=2021-09-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2030803, encodeId=5e36203080388, content=<a href='/topic/show?id=71353e8964f' target=_blank style='color:#2F92EE;'>#发生发展#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37896, encryptionId=71353e8964f, topicName=发生发展)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=346311, createdName=wgsun, createdTime=Sun Mar 21 17:23:57 CST 2021, time=2021-03-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1372438, encodeId=47e213e243866, content=<a href='/topic/show?id=9d861362e53' target=_blank style='color:#2F92EE;'>#p53#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13627, encryptionId=9d861362e53, topicName=p53)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5d70341, createdName=zhishijing, createdTime=Mon Dec 28 15:23:57 CST 2020, time=2020-12-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1531710, encodeId=fe311531e104e, content=<a href='/topic/show?id=770e5e9457' target=_blank style='color:#2F92EE;'>#Death#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5794, encryptionId=770e5e9457, topicName=Death)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=32e312278742, createdName=cy0328, createdTime=Mon Dec 28 15:23:57 CST 2020, time=2020-12-28, status=1, ipAttribution=)]
    2020-12-28 zhishijing
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    2020-12-28 cy0328

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韩宝惠:2020年肺癌靶向治疗进展年终盘点

尽管受新冠肺炎疫情影响,2020年ASCO、ESMO及WCLC等肺癌领域重大线下会议均被取消,但是,本年度仍有众多重磅研究对外公布研究结果。笔者就今年肺癌领域靶向治疗进展进行盘点,与同行一起分享。

Eur J Heart Fail:肺癌、结肠癌或胰腺癌患者室性心动过速、室性早搏和死亡率的关系

结直肠癌、胰腺癌和非小细胞肺癌患者,非持续性室性心动过速更为常见,并且与PVC一起可预测长期死亡率。这提高了心血管死亡率成为某些癌症未来治疗干预目标的可能性。

J Thromb Haemost:ALK和EGFR突变型肺癌患者血栓栓塞风险分析

ALK突变晚期肺腺癌患者的TE发生率最高。TE与各种分子亚型癌症患者较差的生存结局有关,在进行血栓预防的决策时应考虑这些结果。

大医生争相治肺癌,这种高发病无人问津!病人长期忍受身心痛苦

12月5日,中国胸壁外科联盟大会在广州召开。为了唤起全社会对胸壁健康的关注,联盟倡议将每年的5月9日设立为“胸壁关爱日”。

Brit J Cancer:二甲双胍与肺癌患者生存率的关系

二甲双胍可提高LC患者生存率,尤其是区域性SCC患者的LCSS。需要进一步的前瞻性研究来明确二甲双胍在LC治疗中的作用。

Br J Cancer:TNIK抑制剂NCB-0846阻断TGFβ/SMAD信号通路抑制肺癌的转移

癌症的转移是癌症患者死亡的主要原因,目前仍是临床肿瘤学的一大主要挑战。上皮-间质转化(EMT)最初是在胚胎发育中提出的,越来越的的研究显示在癌症的转移过程中EMT起着至关重要的作用。