Cell death &differ:CR1调控结肠癌肿瘤干细胞功能

2015-03-23 佚名 生物谷

近日,国际期刊cell death&differentiation 在线发表了意大利科学家的一项最新研究进展,他们发现胚胎期蛋白Cripto-1(CR1)在结肠癌肿瘤干细胞中表达能够促进肿瘤干细胞的克隆形成,这项研究表明CR1可能通过促进结肠癌肿瘤干细胞生长导致结肠癌复发。 最近,细胞干性被描述为一种动态变化,在正常细胞和肿瘤细胞中都可能存在。研究人员发现胚胎期蛋白Cripto-1(CR1)

近日,国际期刊cell death&differentiation 在线发表了意大利科学家的一项最新研究进展,他们发现胚胎期蛋白Cripto-1(CR1)在结肠癌肿瘤干细胞中表达能够促进肿瘤干细胞的克隆形成,这项研究表明CR1可能通过促进结肠癌肿瘤干细胞生长导致结肠癌复发。

最近,细胞干性被描述为一种动态变化,在正常细胞和肿瘤细胞中都可能存在。研究人员发现胚胎期蛋白Cripto-1(CR1)能够在结肠隐窝底部的正常干细胞中表达,同时也表达在结肠癌组织的肿瘤干细胞中。通过对结肠癌病人的肿瘤组织进行分选,找到CR1阳性的细胞亚群,研究人员发现这群细胞具有更强的克隆形成能力同时表达干细胞相关性基因。

CR1在肿瘤细胞中的表达随时间发生变化,受到细胞内蛋白,细胞表面蛋白和分泌蛋白的复杂调控,并且这些调控作用都与CR1阳性亚群的克隆形成能力具有相关性。在体外实验中抑制CR1表达能够诱导肿瘤干细胞生长暂停,这种抑制伴随着Src/Akt信号途径的作用下调,而通过体内实验也证明,沉默CR1能够抑制CSC驱动的肿瘤移植物生长并能够减少肿瘤干细胞的数目。利用诱导型表达系统在已经建立的肿瘤移植物中沉默CR1能够抑制肿瘤干细胞生长,并且这种抑制效应在原发性肿瘤和转移性肿瘤中均存在,这都证明了CR1对肿瘤干细胞生长具有重要调控作用。

这些结果表明CR1是调节结肠癌肿瘤干细胞功能一个新的动态调控因子,未来或可成为治疗结肠癌,抑制肿瘤干细胞功能,防止癌症复发的一个重要靶向基因。

原始出处:

F Francescangeli1,2, P Contavalli,et al.Dynamic regulation of the cancer stem cell compartment by Cripto-1 in colorectal cancer[J].Cell Death and Differentiation,March 20, 2015.doi: 10.1038/cdd.2015.19.

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    2015-07-20 维他命
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    2015-09-28 isabellayj
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    2015-03-25 cy0328
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