Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41388-017-0038-6
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dc.titleGNA13 expression promotes drug resistance and tumor-initiating phenotypes in squamous cell cancers
dc.contributor.authorRasheed, S.A.K
dc.contributor.authorLeong, H.S
dc.contributor.authorLakshmanan, M
dc.contributor.authorRaju, A
dc.contributor.authorDadlani, D
dc.contributor.authorChong, F.-T
dc.contributor.authorShannon, N.B
dc.contributor.authorRajarethinam, R
dc.contributor.authorSkanthakumar, T
dc.contributor.authorTan, E.Y
dc.contributor.authorHwang, J.S.G
dc.contributor.authorLim, K.H
dc.contributor.authorTan, D.S.-W
dc.contributor.authorCeppi, P
dc.contributor.authorWang, M
dc.contributor.authorTergaonkar, V
dc.contributor.authorCasey, P.J
dc.contributor.authorIyer, N.G
dc.date.accessioned2020-09-09T04:10:54Z
dc.date.available2020-09-09T04:10:54Z
dc.date.issued2018
dc.identifier.citationRasheed, S.A.K, Leong, H.S, Lakshmanan, M, Raju, A, Dadlani, D, Chong, F.-T, Shannon, N.B, Rajarethinam, R, Skanthakumar, T, Tan, E.Y, Hwang, J.S.G, Lim, K.H, Tan, D.S.-W, Ceppi, P, Wang, M, Tergaonkar, V, Casey, P.J, Iyer, N.G (2018). GNA13 expression promotes drug resistance and tumor-initiating phenotypes in squamous cell cancers. Oncogene 37 (10) : 1340-1353. ScholarBank@NUS Repository. https://doi.org/10.1038/s41388-017-0038-6
dc.identifier.issn0950-9232
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/175123
dc.description.abstractTreatment failure in solid tumors occurs due to the survival of specific subpopulations of cells that possess tumor-initiating (TIC) phenotypes. Studies have implicated G protein-coupled-receptors (GPCRs) in cancer progression and the acquisition of TIC phenotypes. Many of the implicated GPCRs signal through the G protein GNA13. In this study, we demonstrate that GNA13 is upregulated in many solid tumors and impacts survival and metastases in patients. GNA13 levels modulate drug resistance and TIC-like phenotypes in patient-derived head and neck squamous cell carcinoma (HNSCC) cells in vitro and in vivo. Blockade of GNA13 expression, or of select downstream pathways, using small-molecule inhibitors abrogates GNA13-induced TIC phenotypes, rendering cells vulnerable to standard-of-care cytotoxic therapies. Taken together, these data indicate that GNA13 expression is a potential prognostic biomarker for tumor progression, and that interfering with GNA13-induced signaling provides a novel strategy to block TICs and drug resistance in HNSCCs. © 2017 The Author(s).
dc.publisherNature Publishing Group
dc.sourceUnpaywall 20200831
dc.subjectantineoplastic agent
dc.subjectcisplatin
dc.subjectcytotoxic agent
dc.subjectGNA13 protein
dc.subjectGNA13 protein inhibitor
dc.subjectguanine nucleotide binding protein
dc.subjectprotein inhibitor
dc.subjecttumor marker
dc.subjectunclassified drug
dc.subjectantineoplastic agent
dc.subjectguanine nucleotide binding protein alpha subunit
dc.subjecttumor marker
dc.subjectanimal cell
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectArticle
dc.subjectcancer growth
dc.subjectcancer patient
dc.subjectcancer prognosis
dc.subjectcancer resistance
dc.subjectcancer survival
dc.subjectcarcinoma cell
dc.subjectcontrolled study
dc.subjecthead and neck squamous cell carcinoma
dc.subjecthuman
dc.subjecthuman cell
dc.subjectin vitro study
dc.subjectin vivo study
dc.subjectmetastasis
dc.subjectmouse
dc.subjectnonhuman
dc.subjectphenotype
dc.subjectpriority journal
dc.subjectprotein expression
dc.subjectprotein function
dc.subjectrandomized controlled trial
dc.subjectsignal transduction
dc.subjectsolid malignant neoplasm
dc.subjecttumor initiating phenotype
dc.subjectupregulation
dc.subjectanimal
dc.subjectcell proliferation
dc.subjectcell transformation
dc.subjectdrug effect
dc.subjectdrug resistance
dc.subjectdrug therapy
dc.subjectgene expression regulation
dc.subjectgenetics
dc.subjectnonobese diabetic mouse
dc.subjectpathology
dc.subjectphenotype
dc.subjectSCID mouse
dc.subjecttumor cell culture
dc.subjectAnimals
dc.subjectAntineoplastic Agents
dc.subjectBiomarkers, Tumor
dc.subjectCell Proliferation
dc.subjectCell Transformation, Neoplastic
dc.subjectDrug Resistance, Neoplasm
dc.subjectGene Expression Regulation, Neoplastic
dc.subjectGTP-Binding Protein alpha Subunits
dc.subjectHumans
dc.subjectMice
dc.subjectMice, Inbred NOD
dc.subjectMice, SCID
dc.subjectPhenotype
dc.subjectSignal Transduction
dc.subjectSquamous Cell Carcinoma of Head and Neck
dc.subjectTumor Cells, Cultured
dc.typeArticle
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.description.doi10.1038/s41388-017-0038-6
dc.description.sourcetitleOncogene
dc.description.volume37
dc.description.issue10
dc.description.page1340-1353
dc.published.statePublished
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