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NSD1支持细胞生长,并调节HPV阴性头支状细胞癌的自性

Iuliia Topchu¹, Igor Bychkov^1,2, Demirkan Gursel³

¹Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Division of Hematology/Oncology, Northwestern University, Chicago, IL, 60611, USA.

Cell death discovery

|February 12, 2024

概括

头部和部状细胞癌 (HNSCC) 涉及NSD1基因,该基因通过激活Akt/mTORC1信号和自来驱动瘤生长. 准NSD1可能为HPV阴性HNSCC提供新的治疗策略.

科学领域:

在瘤学瘤学.
分子生物学分子生物学
癌症研究癌症研究

背景情况:

头部和部状细胞癌 (HNSCC) 是一种流行癌症,持续5年生存率约为66%.
识别HPV阴性HNSCC的驱动因素对于开发向疗法和改善患者治疗结果至关重要.
基因组甲基转移酶NSD1与HNSCC有关,失活突变与更好的预后相关.

研究的目的:

调查NSD1在调节细胞生长,信号通路和HNSCC.自中的作用.
为了确定NSD1是否作为头癌的潜在治疗标.

主要方法:

在HNSCC细胞系和体内模型中NSD1的耗尽.
对细胞生长,Akt/mTORC1信号通路激活和自基因表达的分析.
评估p62,LC3B-II和ULK1的蛋白质含量,并评估自流量.

主要成果:

在体外和体内,NSD1的减弱显著减少了HNSCC细胞的生长.
发现NSD1促进了Akt/mTORC1信号通路的激活.
导致自基因程序,改变了蛋白质水平 (p62,LC3B-II,ULK1),并破坏了自流.

结论:

在HNSCC中,NSD1积极调节Akt/mTORC1信号和自.
这些发现突出了NSD1在头癌中的新功能.
在HNSCC治疗中,NSD1是潜在的治疗点.

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