NAT COMMUN:细胞骨架调节蛋白可驱动胶质母细胞瘤的发生

2020-07-11 MedSci原创 MedSci原创

胶质母细胞瘤是一种致命的癌症,至今为止还没有有效的治疗方法。我们迫切需要更好地了解和确定选择性靶点。

胶质母细胞瘤是一种致命的癌症,至今为止还没有有效的治疗方法。我们迫切需要更好地了解和确定选择性靶点。

最近,研究人员发现,在其测试的所有胶质母细胞瘤中,包括胶质母细胞瘤干细胞/启动细胞中,advillin(AVIL)都过度表达,但该蛋白在非肿瘤星形细胞、神经干细胞或正常脑中几乎检测不到。

AVIL表达增加的胶质瘤患者预后较差。沉默AVIL几乎能根除培养物中的胶质母细胞瘤细胞,并显著抑制小鼠体内异种移植,但对正常对照细胞没有影响。

相反,过表达AVIL促进了细胞的增殖和迁移,使成纤维细胞摆脱了接触抑制,并转化了永生的星形细胞,这支持AVIL蛋白是一个真正的癌基因。

此外,实验证据表明,AVIL的致瘤作用部分是由FOXM1介导的,FOXM1调控LIN28B,LIN28B的表达也与临床预后相关。

AVIL通过调控F-actin来调节细胞骨架,而破坏F-actin结合的突变体在其致瘤能力上存在缺陷。

 

原始出处:

Zhongqiu Xie et al. A cytoskeleton regulator AVIL drives tumorigenesis in glioblastoma, Nature Communications (2020). 

 

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    2021-01-05 liye789132251
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    2020-11-16 liuli5079
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