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 sequencing. 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 sequencing 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.

肿瘤的转录分析揭示了癌细胞中的一种类似压力的状态，伴随着fos , jun等基因的协同表达。和热休克蛋白，尽管考虑到与单细胞 RNA 测序相关的可能解离效应，这一直存在争议。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从肿瘤发生的早期阶段就存在。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 测序数据集相比，表明在肿瘤发生过程中这种状态是保守的。我们还提供证据表明这种状态具有更高的肿瘤播种能力，并且在 MEK 和 BRAF 抑制剂下，它的诱导导致生长增加。总的来说，