ArticleScience signaling2016
MET signaling in keratinocytes activates EGFR and initiates squamous carcinogenesis.
Article in Science signaling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- BRAF Inhibition and UVB Light Synergistically PromoteCancers · 2024Article
- Polypharmacology-based kinome screen identifies new regulators of KSHV reactivation.PLoS pathogens · 2023Article
- Polypharmacology-based kinome screen identifies new regulators of KSHV reactivation.bioRxiv : the preprint server for biology · 2023Article
- Oncogenic Ras and ΔNp63α cooperate to recruit immunosuppressive polymorphonuclear myeloid-derived suppressor cells in a mouse model of squamous cancer pathogenesis.Frontiers in immunology · 2023Article
- RAS oncogene signal strength regulates matrisomal gene expression and tumorigenicity of mouse keratinocytes.Carcinogenesis · 2022Article
- Loss of Tpl2 activates compensatory signaling and resistance to EGFR/MET dual inhibition in v-RAS transduced keratinocytes.PloS one · 2022Article
- Transglutaminase 2 Maintains Hepatocyte Growth Factor Signaling to Enhance the Cancer Cell Phenotype.Molecular cancer research : MCR · 2021Article
- The complexities of PKCα signaling in cancer.Advances in biological regulation · 2021Review
- iRhom2: An Emerging Adaptor Regulating Immunity and Disease.International journal of molecular sciences · 2020Review
- The Identification of Potential Therapeutic Targets for Cutaneous Squamous Cell Carcinoma.The Journal of investigative dermatology · 2020Article
- Autophagy Regulatory Genes MET and RIPK2 Play a Prognostic Role in Pancreatic Ductal Adenocarcinoma: A Bioinformatic Analysis Based on GEO and TCGA.BioMed research international · 2020Article
- Upregulation of miR-340 Inhibits Tumor Growth and Mesenchymal Transition via Targeting c-MET in Glioblastoma.Cancer management and research · 2020Article
- Association of iRhom1 and iRhom2 expression with prognosis in patients with cervical cancer and possible signaling pathways.Oncology reports · 2020Article
- T-Cell Deletion of MyD88 Connects IL17 and IκBζ to RAS Oncogenesis.Molecular cancer research : MCR · 2019Article
- Inhibition of HGF/MET signaling decreases overall tumor burden and blocks malignant conversion in Tpl2-related skin cancer.Oncogenesis · 2019Article
- Human rhomboid family-1 modulates clathrin coated vesicle-dependent pro-transforming growth factor α membrane trafficking to promote breast cancer progression.EBioMedicine · 2018Article
- MicroRNA-7-5p mediates the signaling of hepatocyte growth factor to suppress oncogenes in the MCF-10A mammary epithelial cell.Scientific reports · 2017Article
- Cancer Transcriptome Dataset Analysis: Comparing Methods of Pathway and Gene Regulatory Network-Based Cluster Identification.Omics : a journal of integrative biology · 2017Article
- Cell autonomous or systemic EGFR blockade alters the immune-environment in squamous cell carcinomas.International journal of cancer · 2016Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
The receptor tyrosine kinase MET is abundant in many human squamous cell carcinomas (SCCs), but its functional significance in tumorigenesis is not clear. We found that the incidence of carcinogen-induced skin squamous tumors was substantially increased in transgenic MT-HGF (mouse metallothionein-hepatocyte growth factor) mice, which have increased abundance of the MET ligand HGF. Squamous tumors also erupted spontaneously on the skin of MT-HGF mice that were promoted by wounding or the application of 12-O-tetradecanoylphorbol 13-acetate, an activator of protein kinase C. Carcinogen-initiated tumors had Ras mutations, but spontaneous tumors did not. Cultured keratinocytes from MT-HGF mice and oncogenic RAS-transduced keratinocytes shared phenotypic and biochemical features of initiation that were dependent on autocrine activation of epidermal growth factor receptor (EGFR) through increased synthesis and release of EGFR ligands, which was mediated by the kinase SRC, the pseudoproteases iRhom1 and iRhom2, and the metallopeptidase ADAM17. Pharmacological inhibition of EGFR caused the regression of MT-HGF squamous tumors that developed spontaneously in orthografts of MT-HGF keratinocytes combined with dermal fibroblasts and implanted onto syngeneic mice. The global gene expression profile in MET-transformed keratinocytes was highly concordant with that in RAS-transformed keratinocytes, and a core RAS/MET coexpression network was activated in precancerous and cancerous human skin lesions. Tissue arrays revealed that many human skin SCCs have abundant HGF at both the transcript and protein levels. Thus, through the activation of EGFR, MET activation parallels a RAS pathway to contribute to human and mouse cutaneous cancers.
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