Nat Gene:“突变”细胞相互竞争,有助预防癌症

2020-05-22 竹子 转化医学网

导言:克隆体是由单个干细胞通过正常细胞分裂而形成的的细胞群落。人体组织由克隆体拼凑的,在整个生命周期中自然发生的DNA 的突变,会从父母传递到子代细胞中。一些DNA突变,特别是那些影响“准

导言:克隆体是由单个干细胞通过正常细胞分裂而形成的的细胞群落。人体组织由克隆体拼凑的,在整个生命周期中自然发生的DNA 的突变,会从父母传递到子代细胞中。一些DNA突变,特别是那些影响“准癌细胞”的突变,例如TP53和NOTCH1,赋予获得它们的细胞竞争优势。这使得这些突变克隆体比正常细胞更迅速地扩增,并可能导致疾病。到中年,像食管和皮肤等组织中的大多数细胞都是突变克隆体。但尽管如此,绝大多数人仍未继续形成癌症。惠康桑格研究所的一项先前研究表明,彼此竞争的克隆体有助于预防癌症的形成,但是直到现在,克隆竞争的“游戏规则”还是未知的。

惠康桑格研究所、剑桥大学及其合作者的一项研究发现,可能导致癌症的“突变”细胞的扩增通常受到“邻居”的控制。研究小组发现,当小鼠食道中相匹配的细胞同时出现时,它们会阻碍彼此的生长。这项最近发表在《自然遗传学》上的研究,首次描述了食道细胞之间竞争的“游戏规则” 。通过了解这些规则,希望可以开发出治疗方法,以降低更可能癌变的突变克隆细胞的竞争力。

为了发现突变克隆体之间的相互作用,研究人员结合了遗传谱系追踪和超深测序,观察了小鼠食道上皮的进化突变情况。用一种称为二乙基亚硝胺(DEN)的诱变剂(一种在烟草烟雾中发现的会引起基因突变的物质),在小鼠体内产生一种类似老年食管组织的突变克隆体。

研究小组发现,突变克隆体的动态取决于它们携带的突变及其相邻细胞的性质。与相似的“健康”细胞碰撞的扩展突变克隆体失去了竞争优势,并恢复了正常组织的平衡生长。

当克隆体获得某些突变时,就好像它们在玩加铅的骰子,而正常细胞玩的是普通骰子。这一小的优势足以帮助它们与其他克隆体竞争,并随着时间的推移在更大的组织区域定居,如果不加以控制,就可能会导致疾病。在食道组织中,该组织充满了携带癌症驱动突变的细胞,实际上,突变克隆体相互抵消,有助于保持组织健康。

在试图解释为什么突变克隆体在具有高突变负荷的组织中继续癌变,人们对克隆体之间是否发生竞争存在一些争论。研究发现表明,竞争不仅发生在食管上皮,而且它有助于维持体内平衡,并抑制携带已知致癌突变的克隆体继续朝着疾病的方向发展。

了解克隆竞争的动态,为设计旨在降低潜在危险克隆体竞争优势的疗法提供了可能性。通过去除这些克隆或防止它们成为优势,可以降低患癌症的风险。

在人体组织中,空间有限,克隆争夺空间,适者生存的规则也适用。如果能对付可能继续形成癌症的“坏”克隆,并支持它们更良性的邻居,那么坏的克隆将被替换。通过了解游戏规则,可以认真考虑如何干预和预防某些癌症的发生。

原始出处:

Bartomeu Colom, Maria P. Alcolea, Gabriel Piedrafita, et.al. Spatial competition shapes the dynamic mutational landscape of normal esophageal epithelium. Nature Genetics 18 May 2020

版权声明:
本网站所有内容来源注明为“梅斯医学”或“MedSci原创”的文字、图片和音视频资料,版权均属于梅斯医学所有。非经授权,任何媒体、网站或个人不得转载,授权转载时须注明来源为“梅斯医学”。其它来源的文章系转载文章,或“梅斯号”自媒体发布的文章,仅系出于传递更多信息之目的,本站仅负责审核内容合规,其内容不代表本站立场,本站不负责内容的准确性和版权。如果存在侵权、或不希望被转载的媒体或个人可与我们联系,我们将立即进行删除处理。
在此留言
评论区 (4)
#插入话题
  1. [GetPortalCommentsPageByObjectIdResponse(id=1884334, encodeId=ed4e18843348a, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Tue Jul 14 11:01:55 CST 2020, time=2020-07-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2049299, encodeId=d548204929912, content=<a href='/topic/show?id=4363e929ad' target=_blank style='color:#2F92EE;'>#Gene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7929, encryptionId=4363e929ad, topicName=Gene)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=63a4277, createdName=cy0324, createdTime=Sat Sep 12 22:01:55 CST 2020, time=2020-09-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1488071, encodeId=17e114880e123, content=<a href='/topic/show?id=5c699e46010' target=_blank style='color:#2F92EE;'>#防癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97460, encryptionId=5c699e46010, topicName=防癌)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f6d78400961, createdName=jeanqiuqiu, createdTime=Sun May 24 00:01:55 CST 2020, time=2020-05-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=383046, encodeId=a04a3830468d, content=如果能够干预癌症的发生,那简直就是奇迹, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2019/01/04/5a983eec2c4de0503b3442d17bd485f6.jpg, createdBy=99d92511839, createdName=124bf027m33暂无昵称, createdTime=Fri May 22 13:16:25 CST 2020, time=2020-05-22, status=1, ipAttribution=)]
    2020-07-14 liye789132251
  2. [GetPortalCommentsPageByObjectIdResponse(id=1884334, encodeId=ed4e18843348a, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Tue Jul 14 11:01:55 CST 2020, time=2020-07-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2049299, encodeId=d548204929912, content=<a href='/topic/show?id=4363e929ad' target=_blank style='color:#2F92EE;'>#Gene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7929, encryptionId=4363e929ad, topicName=Gene)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=63a4277, createdName=cy0324, createdTime=Sat Sep 12 22:01:55 CST 2020, time=2020-09-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1488071, encodeId=17e114880e123, content=<a href='/topic/show?id=5c699e46010' target=_blank style='color:#2F92EE;'>#防癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97460, encryptionId=5c699e46010, topicName=防癌)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f6d78400961, createdName=jeanqiuqiu, createdTime=Sun May 24 00:01:55 CST 2020, time=2020-05-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=383046, encodeId=a04a3830468d, content=如果能够干预癌症的发生,那简直就是奇迹, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2019/01/04/5a983eec2c4de0503b3442d17bd485f6.jpg, createdBy=99d92511839, createdName=124bf027m33暂无昵称, createdTime=Fri May 22 13:16:25 CST 2020, time=2020-05-22, status=1, ipAttribution=)]
    2020-09-12 cy0324
  3. [GetPortalCommentsPageByObjectIdResponse(id=1884334, encodeId=ed4e18843348a, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Tue Jul 14 11:01:55 CST 2020, time=2020-07-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2049299, encodeId=d548204929912, content=<a href='/topic/show?id=4363e929ad' target=_blank style='color:#2F92EE;'>#Gene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7929, encryptionId=4363e929ad, topicName=Gene)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=63a4277, createdName=cy0324, createdTime=Sat Sep 12 22:01:55 CST 2020, time=2020-09-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1488071, encodeId=17e114880e123, content=<a href='/topic/show?id=5c699e46010' target=_blank style='color:#2F92EE;'>#防癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97460, encryptionId=5c699e46010, topicName=防癌)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f6d78400961, createdName=jeanqiuqiu, createdTime=Sun May 24 00:01:55 CST 2020, time=2020-05-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=383046, encodeId=a04a3830468d, content=如果能够干预癌症的发生,那简直就是奇迹, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2019/01/04/5a983eec2c4de0503b3442d17bd485f6.jpg, createdBy=99d92511839, createdName=124bf027m33暂无昵称, createdTime=Fri May 22 13:16:25 CST 2020, time=2020-05-22, status=1, ipAttribution=)]
    2020-05-24 jeanqiuqiu
  4. [GetPortalCommentsPageByObjectIdResponse(id=1884334, encodeId=ed4e18843348a, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Tue Jul 14 11:01:55 CST 2020, time=2020-07-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2049299, encodeId=d548204929912, content=<a href='/topic/show?id=4363e929ad' target=_blank style='color:#2F92EE;'>#Gene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7929, encryptionId=4363e929ad, topicName=Gene)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=63a4277, createdName=cy0324, createdTime=Sat Sep 12 22:01:55 CST 2020, time=2020-09-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1488071, encodeId=17e114880e123, content=<a href='/topic/show?id=5c699e46010' target=_blank style='color:#2F92EE;'>#防癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97460, encryptionId=5c699e46010, topicName=防癌)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f6d78400961, createdName=jeanqiuqiu, createdTime=Sun May 24 00:01:55 CST 2020, time=2020-05-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=383046, encodeId=a04a3830468d, content=如果能够干预癌症的发生,那简直就是奇迹, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2019/01/04/5a983eec2c4de0503b3442d17bd485f6.jpg, createdBy=99d92511839, createdName=124bf027m33暂无昵称, createdTime=Fri May 22 13:16:25 CST 2020, time=2020-05-22, status=1, ipAttribution=)]
    2020-05-22 124bf027m33暂无昵称

    如果能够干预癌症的发生,那简直就是奇迹

    0

相关资讯

国家药监局优先审评审批,新一代国产肺癌创新药上市

新一代国产肺癌创新药“阿美替尼”正式上市。

感谢复工体检偶遇热心医生,一句“问医”助力患者躲过“癌劫”

“感谢市六医院多学科医护人员的搭救之恩,否则肠道肿瘤肆意侵润,自己还蒙在鼓里。”家住浠水返汉务工的53岁吴秀芳(化名)对记者说道,复工体检后,自己不经意间的一句腹部偶尔隐隐胀痛

Nature子刊:禁食+维生素C+化疗的三联疗法对难治疗的癌症有效

5月11日发表在《自然通讯》上的研究表明,禁食与维生素C的结合对难治疗的癌症有效果。

J INTERN MED:房颤伴有癌症患者缺血性卒中后口服抗凝药的使用情况

在过去十年中,口服抗凝剂(OAC)的房颤(AF)患者数量有所增加。近日,内科学领域权威杂志Journal of Internal Medicine上发表一篇研究文章,研究人员旨在描述AF和活动性癌症患

重大突破!《自然》杂志:T细胞免疫疗法完全治愈晚期癌症

人类最好的药物,便是自己的免疫系统。如果彻底用好它,我们甚至可以战胜晚期癌症!

Cell Death Dis:冷等离子体诱导肿瘤细胞死亡的机制

在癌症治疗研究中,电离辐射以外的能够有效杀死癌细胞的新物理技术一直是一个研究热点。冷等离子体(CAP)是一种接近室温的电离气体,由反应性物质、离子、电子、中性粒子、紫外线、可见光等组成。在过去的十年研