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Please use this identifier to cite or link to this item: https://doi.org/10.1038/ncomms12493
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dc.titleInactivation of TGF? receptors in stem cells drives cutaneous squamous cell carcinoma
dc.contributor.authorCammareri, P
dc.contributor.authorRose, A.M
dc.contributor.authorVincent, D.F
dc.contributor.authorWang, J
dc.contributor.authorNagano, A
dc.contributor.authorLibertini, S
dc.contributor.authorRidgway, R.A
dc.contributor.authorAthineos, D
dc.contributor.authorCoates, P.J
dc.contributor.authorMcHugh, A
dc.contributor.authorPourreyron, C
dc.contributor.authorDayal, J.H.S
dc.contributor.authorLarsson, J
dc.contributor.authorWeidlich, S
dc.contributor.authorSpender, L.C
dc.contributor.authorSapkota, G.P
dc.contributor.authorPurdie, K.J
dc.contributor.authorProby, C.M
dc.contributor.authorHarwood, C.A
dc.contributor.authorLeigh, I.M
dc.contributor.authorClevers, H
dc.contributor.authorBarker, N
dc.contributor.authorKarlsson, S
dc.contributor.authorPritchard, C
dc.contributor.authorMarais, R
dc.contributor.authorChelala, C
dc.contributor.authorSouth, A.P
dc.contributor.authorSansom, O.J
dc.contributor.authorInman, G.J
dc.date.accessioned2020-10-31T11:27:40Z
dc.date.available2020-10-31T11:27:40Z
dc.date.issued2016
dc.identifier.citationCammareri, P, Rose, A.M, Vincent, D.F, Wang, J, Nagano, A, Libertini, S, Ridgway, R.A, Athineos, D, Coates, P.J, McHugh, A, Pourreyron, C, Dayal, J.H.S, Larsson, J, Weidlich, S, Spender, L.C, Sapkota, G.P, Purdie, K.J, Proby, C.M, Harwood, C.A, Leigh, I.M, Clevers, H, Barker, N, Karlsson, S, Pritchard, C, Marais, R, Chelala, C, South, A.P, Sansom, O.J, Inman, G.J (2016). Inactivation of TGF? receptors in stem cells drives cutaneous squamous cell carcinoma. Nature Communications 7 : 12493. ScholarBank@NUS Repository. https://doi.org/10.1038/ncomms12493
dc.identifier.issn2041-1723
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/182434
dc.description.abstractMelanoma patients treated with oncogenic BRAF inhibitors can develop cutaneous squamous cell carcinoma (cSCC) within weeks of treatment, driven by paradoxical RAS/RAF/MAPK pathway activation. Here we identify frequent TGFBR1 and TGFBR2 mutations in human vemurafenib-induced skin lesions and in sporadic cSCC. Functional analysis reveals these mutations ablate canonical TGF? Smad signalling, which is localized to bulge stem cells in both normal human and murine skin. MAPK pathway hyperactivation (through Braf V600E or Kras G12D knockin) and TGF? signalling ablation (through Tgfbr1 deletion) in LGR5 +ve stem cells enables rapid cSCC development in the mouse. Mutation of Tp53 (which is commonly mutated in sporadic cSCC) coupled with Tgfbr1 deletion in LGR5 +ve cells also results in cSCC development. These findings indicate that LGR5 +ve stem cells may act as cells of origin for cSCC, and that RAS/RAF/MAPK pathway hyperactivation or Tp53 mutation, coupled with loss of TGF? signalling, are driving events of skin tumorigenesis. © The Author(s) 2016.
dc.publisherNature Publishing Group
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceUnpaywall 20201031
dc.subjectB Raf kinase
dc.subjectK ras protein
dc.subjectmitogen activated protein kinase
dc.subjectSmad2 protein
dc.subjectSmad3 protein
dc.subjectSmad4 protein
dc.subjecttransforming growth factor beta receptor 1
dc.subjecttransforming growth factor beta receptor 2
dc.subjectantineoplastic agent
dc.subjectB Raf kinase
dc.subjectindole derivative
dc.subjectprotein p21
dc.subjectprotein p53
dc.subjectprotein serine threonine kinase
dc.subjectsulfonamide
dc.subjectTGF-beta type I receptor
dc.subjecttransforming growth factor beta
dc.subjecttransforming growth factor beta receptor
dc.subjecttransforming growth factor-beta type II receptor
dc.subjectvemurafenib
dc.subjectcancer
dc.subjectcells and cell components
dc.subjectcytology
dc.subjectgene
dc.subjectgenetic engineering
dc.subjectmutation
dc.subjectprotein
dc.subjectrodent
dc.subjectskin
dc.subjecttumor
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectArticle
dc.subjectcontrolled study
dc.subjectdisease course
dc.subjectextracellular matrix
dc.subjectfemale
dc.subjectgene mutation
dc.subjecthuman
dc.subjecthuman tissue
dc.subjectmale
dc.subjectmouse
dc.subjectnonhuman
dc.subjectsignal transduction
dc.subjectskin carcinogenesis
dc.subjectskin carcinoma
dc.subjectstem cell
dc.subjectanimal
dc.subjectantagonists and inhibitors
dc.subjectbiopsy
dc.subjectcarcinogenesis
dc.subjectchemically induced
dc.subjectdna mutational analysis
dc.subjectdrug effect
dc.subjectexperimental neoplasm
dc.subjectgenetics
dc.subjectinbred mouse strain
dc.subjectmelanoma
dc.subjectmetabolism
dc.subjectmutation
dc.subjectpathology
dc.subjectprocedures
dc.subjectskin tumor
dc.subjectsquamous cell carcinoma
dc.subjectstem cell
dc.subjecttumor cell line
dc.subjectwhole exome sequencing
dc.subjectMurinae
dc.subjectAnimals
dc.subjectAntineoplastic Agents
dc.subjectBiopsy
dc.subjectCarcinogenesis
dc.subjectCarcinoma, Squamous Cell
dc.subjectCell Line, Tumor
dc.subjectDNA Mutational Analysis
dc.subjectFemale
dc.subjectHumans
dc.subjectIndoles
dc.subjectMale
dc.subjectMelanoma
dc.subjectMice
dc.subjectMice, Inbred Strains
dc.subjectMutation
dc.subjectNeoplasms, Experimental
dc.subjectProtein-Serine-Threonine Kinases
dc.subjectProto-Oncogene Proteins B-raf
dc.subjectProto-Oncogene Proteins p21(ras)
dc.subjectReceptors, Transforming Growth Factor beta
dc.subjectSignal Transduction
dc.subjectSkin Neoplasms
dc.subjectStem Cells
dc.subjectSulfonamides
dc.subjectTransforming Growth Factor beta
dc.subjectTumor Suppressor Protein p53
dc.subjectWhole Exome Sequencing
dc.typeArticle
dc.contributor.departmentBIOCHEMISTRY
dc.description.doi10.1038/ncomms12493
dc.description.sourcetitleNature Communications
dc.description.volume7
dc.description.page12493
dc.published.statepublished
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