The Stress-Like Cancer Cell State Is a Consistent Component of Tumorigenesis.
The Stress-Like Cancer Cell State Is a Consistent Component of Tumorigenesis.
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DOI：
10.1016/j.cels.2020.08.018
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发表时间：
2020-11-18
期刊：
影响因子：
9.3
通讯作者：
Yanai I
中科院分区：
文献类型：
--
作者：
Baron M;Tagore M;Hunter MV;Kim IS;Moncada R;Yan Y;Campbell NR;White RM;Yanai I
肿瘤的转录谱分析揭示了癌细胞中的应激样状态，其中基因如fos，jun和热休克蛋白的协同表达，尽管这一直存在争议，因为与单细胞RNA-Seq相关的可能的解离效应。在这里，我们使用斑马鱼黑色素瘤建模，空间转录组学和人类样本的组合来验证这种状态的存在。我们发现，癌细胞的应激样亚群存在于肿瘤发生的早期阶段。与先前报道的来自不同癌症类型（包括三阴性乳腺癌、少突胶质细胞瘤和胰腺癌）的单细胞RNA-Seq数据集相比，表明这种状态在肿瘤发生期间是保守的。我们还提供了证据表明，这种状态具有更高的肿瘤播种能力，并且其诱导导致MEK和BRAF抑制剂下的生长增加。总的来说，我们的研究支持压力样细胞作为一种癌细胞状态，表达一组连贯的基因，并表现出耐药性。在黑色素瘤癌细胞中存在多种转录状态，其中之一是跨物种和其他癌症类型保守的应激样状态。应激样状态在肿瘤进展和药物反应中起作用。
Transcriptional profiling of tumors has revealed a stress-like state among the cancer cells, with the concerted expression of genes such as fos, jun and heat-shock proteins, though this has been controversial given possible dissociation-effects associated with single-cell RNA-Seq. Here, we validate the existence of this state using a combination of zebrafish melanoma modeling, spatial transcriptomics and human samples. We found that the stress-like subpopulation of cancer cells is present from the early stages of tumorigenesis. Comparing with previously reported single-cell RNA-Seq datasets from diverse cancer types, including triple-negative breast cancer, oligodendroglioma and pancreatic adenocarcinoma, indicated the conservation of this state during tumorigenesis. We also provide evidence that this state has higher tumor-seeding capabilities and that its induction leads to increased growth under both MEK and BRAF inhibitors. Collectively, our study supports the stress-like cells as a cancer cell state expressing a coherent set of genes and exhibiting drug-resistance properties. Multiple transcriptional states occur in melanoma cancer cells, one of which is a stress-like state that is conserved across species and other cancer types. The stress-like state has a role in tumor progression and drug response.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
9.3
作者：
Baron M;Veres A;Wolock SL;Faust AL;Gaujoux R;Vetere A;Ryu JH;Wagner BK;Shen-Orr SS;Klein AM;Melton DA;Yanai I
通讯作者：
Yanai I
影响因子：
3.5
作者：
Bianchi, Marzia;Giacomini, Elisa;Magnani, Mauro
通讯作者：
Magnani, Mauro
影响因子：
4.7
作者：
Ahmed F;Haass NK
通讯作者：
Haass NK
影响因子：
16.6
作者：
Gao R;Kim C;Sei E;Foukakis T;Crosetto N;Chan LK;Srinivasan M;Zhang H;Meric-Bernstam F;Navin N
通讯作者：
Navin N