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Cell:乳腺癌干细胞两个转录因子Slug和Sox9与肿瘤转移有关

2012-03-10 MedSci MedSci原创

来自美国Whitehead生物医学研究所,麻省理工学院等处的研究人员发表了题为“Slug and Sox9 Cooperatively Determine the Mammary Stem Cell State”的文章,报道了以前未知的肿瘤干细胞调控方式,并指出了其中两种关键转录因子的重要作用,相关成果公布在Cell杂志上。 文章的通讯作者是鼎鼎大名的Robert A.Weinberg教授,

来自美国Whitehead生物医学研究所,麻省理工学院等处的研究人员发表了题为“Slug and Sox9 Cooperatively Determine the Mammary Stem Cell State”的文章,报道了以前未知的肿瘤干细胞调控方式,并指出了其中两种关键转录因子的重要作用,相关成果公布在Cell杂志上。
文章的通讯作者是鼎鼎大名的Robert A.Weinberg教授,其身上笼罩着一道道绚丽的光环:美国科学院院士,世界着名的Whitehead研究所创始人之一,他曾发现了第一个人类癌基因Ras和第一个抑癌基因Rb,他的一系列杰出研究工作已经成为肿瘤研究领域乃至整个医学生物学领域的重要里程碑。
这项由Weinberg研究组最新完成的研究论文主要围绕的是成人干细胞转录调控因子。转录因子(transcription factors,TFs)的调控网络已经成为了目前生命科学研究领域中的一大重点和热点,这些作用元件不仅在体细胞基因表达中扮演了重要角色,对于干细胞的状态的维持等方面也发挥了关键的作用,然而目前对于这一领域,科学家们了解的比较少。
针对这种情况,在这篇文章中,研究人员发现两种转录因子:Slug和Sox9,能合作决定哺乳动物干细胞(MaSC)状态,其中转录因子Slug是Snail锌指转录因子家族成员之一,参与调控胚胎发育和肿瘤的发生,其基因在物种进化过程中比较保守,有高度保守的C2H2型锌指结构域,通过连接到E-box以抑制靶基因的转录。而Sox9目前发现是是胶原蛋白合成过程中的一个重要的转录因子,在软骨的发育、成熟过程中对胶原蛋白有着正向调控的作用。
研究人员发现抑制Slug和Sox9这两个因子中的一个,就会阻断原发性哺乳动物上皮细胞MaSC的活性,反过来,如果瞬时共表达外源性Slug和Sox9,则能促进已分化的管腔细胞重新转换为具有乳腺长期重构能力的MaSCs。
除此之外,研究人员还发现Slug和Sox9这两种的共表达将促进人类乳腺癌细胞的发展,以及转移发生的能力,并导致病患生存率下降,这证明了人类乳腺癌干细胞调控方式与正常小鼠MaSCs调控方式相似。
Weinberg教授去年还曾在Cell杂志上发表文章,介绍了升级版肿瘤细胞十大特征,这篇同样也是与Douglas Hanahan合作的论文长达29页,简述了最近10年肿瘤学中的热点和进展,包括细胞自噬、肿瘤干细胞、肿瘤微环境等等,并且将原有的肿瘤细胞六大特征扩增到了十个,这十个特征具体请见癌研究泰斗又一Cell力作:肿瘤细胞十大特征。

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    2012-11-26 mjldent
  4. [GetPortalCommentsPageByObjectIdResponse(id=1935565, encodeId=e1f6193556526, content=<a href='/topic/show?id=46a723e4521' target=_blank style='color:#2F92EE;'>#乳腺癌干细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=23745, encryptionId=46a723e4521, topicName=乳腺癌干细胞)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdqq.qlogo.cn/qqapp/1103841572/2898B09F0DA89357D0D54A725E611AC7/100, createdBy=fdd32500040, createdName=ms7899726347904398, createdTime=Sat Sep 22 07:10:00 CST 2012, time=2012-09-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1868467, encodeId=c371186846e2a, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Fri Mar 16 16:10:00 CST 2012, time=2012-03-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1747155, encodeId=1a941e4715513, content=<a href='/topic/show?id=832e93345c3' target=_blank style='color:#2F92EE;'>#转录#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=105, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=93345, encryptionId=832e93345c3, topicName=转录)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=58df35929710, createdName=mjldent, createdTime=Mon Nov 26 13:10:00 CST 2012, time=2012-11-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1958680, encodeId=938d1958680ac, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=82, 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=Tue May 22 01:10:00 CST 2012, time=2012-05-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=4222, encodeId=d560422205, content=So much info in so few words. Tosloty could learn a lot., beContent=null, objectType=article, channel=null, level=null, likeNumber=176, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=ruthie, createdTime=Mon Apr 23 09:16:00 CST 2012, time=2012-04-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1291600, encodeId=47ff1291600c2, content=<a href='/topic/show?id=137a831151a' target=_blank style='color:#2F92EE;'>#肿瘤转移#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=94, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83115, encryptionId=137a831151a, topicName=肿瘤转移)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1be8234, createdName=sunyl07, createdTime=Mon Mar 12 12:10:00 CST 2012, time=2012-03-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1537437, encodeId=3b00153e4374e, content=<a href='/topic/show?id=798a93348bb' target=_blank style='color:#2F92EE;'>#转录因子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=91, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=93348, encryptionId=798a93348bb, topicName=转录因子)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b8c712868269, createdName=lanyan20020090, createdTime=Mon Mar 12 12:10:00 CST 2012, time=2012-03-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1544946, encodeId=ca8c1544946ad, content=<a href='/topic/show?id=7a0fe1289c2' target=_blank style='color:#2F92EE;'>#癌干细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=86, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=71289, encryptionId=7a0fe1289c2, topicName=癌干细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=340013676140, createdName=1249898am19暂无昵称, createdTime=Mon Mar 12 12:10:00 CST 2012, time=2012-03-12, status=1, ipAttribution=)]
    2012-05-22 维他命
  5. [GetPortalCommentsPageByObjectIdResponse(id=1935565, encodeId=e1f6193556526, content=<a href='/topic/show?id=46a723e4521' target=_blank style='color:#2F92EE;'>#乳腺癌干细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=23745, encryptionId=46a723e4521, topicName=乳腺癌干细胞)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdqq.qlogo.cn/qqapp/1103841572/2898B09F0DA89357D0D54A725E611AC7/100, createdBy=fdd32500040, createdName=ms7899726347904398, createdTime=Sat Sep 22 07:10:00 CST 2012, time=2012-09-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1868467, encodeId=c371186846e2a, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Fri Mar 16 16:10:00 CST 2012, time=2012-03-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1747155, encodeId=1a941e4715513, content=<a href='/topic/show?id=832e93345c3' target=_blank style='color:#2F92EE;'>#转录#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=105, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=93345, encryptionId=832e93345c3, topicName=转录)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=58df35929710, createdName=mjldent, createdTime=Mon Nov 26 13:10:00 CST 2012, time=2012-11-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1958680, encodeId=938d1958680ac, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=82, 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=Tue May 22 01:10:00 CST 2012, time=2012-05-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=4222, encodeId=d560422205, content=So much info in so few words. Tosloty could learn a lot., beContent=null, objectType=article, channel=null, level=null, likeNumber=176, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=ruthie, createdTime=Mon Apr 23 09:16:00 CST 2012, time=2012-04-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1291600, encodeId=47ff1291600c2, content=<a href='/topic/show?id=137a831151a' target=_blank style='color:#2F92EE;'>#肿瘤转移#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=94, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83115, encryptionId=137a831151a, topicName=肿瘤转移)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1be8234, createdName=sunyl07, createdTime=Mon Mar 12 12:10:00 CST 2012, time=2012-03-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1537437, encodeId=3b00153e4374e, content=<a href='/topic/show?id=798a93348bb' target=_blank style='color:#2F92EE;'>#转录因子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=91, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=93348, encryptionId=798a93348bb, topicName=转录因子)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b8c712868269, createdName=lanyan20020090, createdTime=Mon Mar 12 12:10:00 CST 2012, time=2012-03-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1544946, encodeId=ca8c1544946ad, content=<a href='/topic/show?id=7a0fe1289c2' target=_blank style='color:#2F92EE;'>#癌干细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=86, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=71289, encryptionId=7a0fe1289c2, topicName=癌干细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=340013676140, createdName=1249898am19暂无昵称, createdTime=Mon Mar 12 12:10:00 CST 2012, time=2012-03-12, status=1, ipAttribution=)]
    2012-04-23 ruthie

    So much info in so few words. Tosloty could learn a lot.

    0

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