Cannabinoids Promote Progression of HPV-Positive Head and Neck Squamous Cell Carcinoma via p38 MAPK Activation
Liu C, Sadat S, Ebisumoto K, Sakai A, Panuganti B, Ren S, Goto Y, Haft S, Fukusumi T, Ando M, Saito Y, Guo T, Tamayo P, Yeerna H, Kim W, Hubbard J, Sharabi A, Gutkind J, Califano J. Cannabinoids Promote Progression of HPV-Positive Head and Neck Squamous Cell Carcinoma via p38 MAPK Activation. Clinical Cancer Research 2020, 26: 2693-2703. PMID: 31932491, PMCID: PMC7538010, DOI: 10.1158/1078-0432.ccr-18-3301.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCannabinoidsCell MovementCell ProliferationFemaleHead and Neck NeoplasmsHumansMiceMice, NudeP38 Mitogen-Activated Protein KinasesPapillomaviridaePapillomavirus InfectionsPrognosisReceptors, CannabinoidSquamous Cell Carcinoma of Head and NeckTumor Cells, CulturedXenograft Model Antitumor AssaysConceptsHead and neck squamous cell carcinomaHPV-positive head and neck squamous cell carcinomaHPV-positive HNSCC cell linesNeck squamous cell carcinomaHNSCC cell linesSingle-sample gene set enrichment analysisSquamous cell carcinomaP38 MAPK pathway activationHNSCC cohortCell carcinomaMAPK pathway activationHPV-negative head and neck squamous cell carcinomaHuman papillomavirus (HPV)-related headCell linesAnimal modelsCannabinoid receptor activationHPV- HNSCC patientsHead and neck squamous cell carcinomas dataMarijuana usePathway activationDaily marijuana useWhole-genome expression analysisCannabinoid exposureHNSCC patientsP38 MAPK activationGαs (GNAS) suppression of the p53 genomic‐stability checkpoint unleashes RAS‐driven oncogenesis
Steffen D, Tiriac H, Valera J, Amornphimoltham P, Kim W, Taylor S, Hunter T, Tamayo P, Gutkind J. Gαs (GNAS) suppression of the p53 genomic‐stability checkpoint unleashes RAS‐driven oncogenesis. The FASEB Journal 2020, 34: 1-1. DOI: 10.1096/fasebj.2020.34.s1.04604.Peer-Reviewed Original ResearchTrp53 tumor suppressor geneCooperation of rasMDM2-mediated p53 ubiquitinationHuman intestinal organoid modelP53 E3 ubiquitin ligaseSquamous cell carcinomaIn vitro ubiquitination assayP53 protein accumulationChemical carcinogen DMBASkin of adult miceTumor suppressor genePhosphorylation of Mdm2Control genome stabilityE3 ubiquitin ligaseRAS mutant tumorsRas-driven oncogenesisCarcinogenesis in vivoSubstrate of PKAConstitutively activating mutationAppendix cancerPan-cancer analysisActivation of signalingPatient sequencing dataBenign tumorsCell carcinoma