PUBLICATION
Oncogenic Ras activation in permissive somatic cells triggers rapid-onset phenotypic plasticity and elicits a tumor-promoting neutrophil response
- Authors
- Elliot, A.M., Ribeiro Bravo, I., Zhao, Y., Wang, Z., Astorga Johansson, J., Hutton, E., Cunningham, R., Myllymäki, H., Chang, K.Y., Cholewa-Waclaw, J., Kelly, L., Beltran, M., Lewis, A., Elks, P.M., Hansen, C.G., Henderson, N.C., Feng, Y.
- ID
- ZDB-PUB-251026-2
- Date
- 2025
- Source
- Cell Reports 44: 116478116478 (Journal)
- Registered Authors
- Feng, Yi
- Keywords
- CP: Cancer, CP: Immunology, Ras, epithelial-mesenchymal transition, preneoplastic, tumor initiation, tumor-associated neutrophils, zebrafish
- MeSH Terms
-
- Animals
- Carcinogenesis/pathology
- Cell Plasticity*
- Cell Proliferation
- Epithelial-Mesenchymal Transition
- Humans
- Keratinocytes/metabolism
- Keratinocytes/pathology
- Neutrophils*/immunology
- Neutrophils*/metabolism
- Neutrophils*/pathology
- Phenotype
- Proto-Oncogene Proteins p21(ras)*/genetics
- Proto-Oncogene Proteins p21(ras)*/metabolism
- Skin Neoplasms/genetics
- Skin Neoplasms/pathology
- Zebrafish
- ras Proteins*/metabolism
- PubMed
- 41138187 Full text @ Cell Rep.
Citation
Elliot, A.M., Ribeiro Bravo, I., Zhao, Y., Wang, Z., Astorga Johansson, J., Hutton, E., Cunningham, R., Myllymäki, H., Chang, K.Y., Cholewa-Waclaw, J., Kelly, L., Beltran, M., Lewis, A., Elks, P.M., Hansen, C.G., Henderson, N.C., Feng, Y. (2025) Oncogenic Ras activation in permissive somatic cells triggers rapid-onset phenotypic plasticity and elicits a tumor-promoting neutrophil response. Cell Reports. 44:116478116478.
Abstract
Oncogenic driver mutations are common in normal tissues, indicating that non-genetic factors are necessary for tumorigenesis. Phenotypic plasticity is a crucial gateway to malignancy, and inflammation can fuel tumorigenesis; however, little is known about the timing and mechanisms by which these hallmarks first emerge. Using single-cell transcriptomics and in vivo live imaging, we characterized the immediate cell-intrinsic and innate immune responses during the first 24 h following oncogenic Ras activation in a zebrafish model of HRASG12V-mediated skin tumor initiation. We found that in a subset of basal keratinocytes, RAS alone drives phenotypic plasticity, and these cells undergo dedifferentiation and partial epithelial-to-mesenchymal transition (EMT), resembling malignant cells in human squamous cell carcinoma. Strikingly, these cells also drive a tumor-promoting neutrophil program, which in turn enhances preneoplastic cell proliferation. Thus, oncogenic Ras effects are dictated by the cell of origin, and we revealed a link between unlocking plasticity and the onset of tumor-promoting inflammation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping