The Stress-Like Cancer Cell State Is a Consistent Component of Tumorigenesis.
IF: 11.091
Cited by: 53


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.


Spatial Transcriptomics
cancer cell states
drug-resistant states
single-cell RNA-seq
spatial transcriptomics

MeSH terms

Cell Line, Tumor
Drug Resistance, Neoplasm
Gene Expression
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Protein Kinase Inhibitors
Sequence Analysis, RNA
Single-Cell Analysis
Stress, Physiological


Baron, Maayan
Tagore, Mohita
Hunter, Miranda V
Kim, Isabella S
Moncada, Reuben
Yan, Yun
Campbell, Nathaniel R
White, Richard M
Yanai, Itai

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