PUBLICATION
The Stress-Like Cancer Cell State Is a Consistent Component of Tumorigenesis
- Authors
- Baron, M., Tagore, M., Hunter, M.V., Kim, I.S., Moncada, R., Yan, Y., Campbell, N.R., White, R.M., Yanai, I.
- ID
- ZDB-PUB-201002-12
- Date
- 2020
- Source
- Cell systems 11(5): 536-546.e7 (Journal)
- Registered Authors
- White, Richard M.
- Keywords
- cancer cell states, drug-resistant states, melanoma, single-cell RNA-seq, spatial transcriptomics, stress-like
- MeSH Terms
-
- Adenocarcinoma/genetics
- Animals
- Carcinogenesis/metabolism
- Carcinogenesis/pathology*
- Cell Line, Tumor
- Drug Resistance, Neoplasm/genetics
- Gene Expression/genetics
- Gene Expression Profiling/methods
- Gene Expression Regulation, Neoplastic/genetics
- Humans
- Melanoma/genetics*
- Melanoma/metabolism
- Melanoma/physiopathology
- Protein Kinase Inhibitors/pharmacology
- Sequence Analysis, RNA/methods
- Single-Cell Analysis/methods
- Stress, Physiological/genetics*
- Transcriptome/genetics
- Zebrafish
- PubMed
- 32910905 Full text @ Cell Syst
Citation
Baron, M., Tagore, M., Hunter, M.V., Kim, I.S., Moncada, R., Yan, Y., Campbell, N.R., White, R.M., Yanai, I. (2020) The Stress-Like Cancer Cell State Is a Consistent Component of Tumorigenesis. Cell systems. 11(5):536-546.e7.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping