Please use this identifier to cite or link to this item: https://doi.org/10.18632/oncotarget.4654
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dc.titleRUNX2 and TAZ-dependent signaling pathways regulate soluble E-Cadherin levels and tumorsphere formation in breast cancer cells
dc.contributor.authorBrusgard, J.L
dc.contributor.authorChoe, M
dc.contributor.authorChumsri, S
dc.contributor.authorRenoud, K
dc.contributor.authorMacKerell, A.D
dc.contributor.authorSudol, M
dc.contributor.authorPassaniti, A
dc.date.accessioned2020-09-03T10:36:45Z
dc.date.available2020-09-03T10:36:45Z
dc.date.issued2015
dc.identifier.citationBrusgard, J.L, Choe, M, Chumsri, S, Renoud, K, MacKerell, A.D, Sudol, M, Passaniti, A (2015). RUNX2 and TAZ-dependent signaling pathways regulate soluble E-Cadherin levels and tumorsphere formation in breast cancer cells. Oncotarget 6 (29) : 28132-28150. ScholarBank@NUS Repository. https://doi.org/10.18632/oncotarget.4654
dc.identifier.issn19492553
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/174137
dc.description.abstractIntratumoral heterogeneity and treatment resistance drive breast cancer (BC) metastasis and recurrence. The RUNX2 transcription factor is upregulated in early stage luminal BC. However, the precise mechanism by which RUNX2 regulates an oncogenic phenotype in luminal BCs remains an enigma. We show that RUNX2 is predictive of poor overall survival in BC patients. RUNX2 associated with the TAZ transcriptional co-activator to promote a tumorigenic phenotype that was inhibited by knockdown of TAZ. RUNX2 increased endogenous TAZ translocation to the nucleus, which was prevented by inhibiting RUNX2. RUNX2/TAZ interaction was associated with ectodomain shedding of an oncogenic soluble E-Cadherin fragment (sE-Cad), which is known to cooperate with human epidermal growth factor receptor-2 (HER2/ ErbB2) to increase BC growth. Neutralizing E-Cadherin antibodies or TAZ knockdown reduced the levels of sE-Cad in RUNX2-expressing BC cells and inhibited tumorsphere formation. RUNX2 expression also increased HER2-mediated tumorsphere size, which was reduced after treatment with the HER2-targeting agents Herceptin and lapatinib. These data support a novel role for RUNX2 in promoting an oncogenic phenotype in luminal BC in the context of TAZ, sE-Cad, and HER2. Using this signaling pathway to monitor BC cell oncogenic activity will accelerate the discovery of new therapeutic modalities to treat BC patients.
dc.sourceUnpaywall 20200831
dc.subjectepidermal growth factor receptor 2
dc.subjectlapatinib
dc.subjectneutralizing antibody
dc.subjecttranscription factor
dc.subjecttranscription factor RUNX2
dc.subjecttranscription factor TAZ
dc.subjecttrastuzumab
dc.subjectunclassified drug
dc.subjectuvomorulin
dc.subjectcadherin
dc.subjectdoxycycline
dc.subjectepidermal growth factor receptor 2
dc.subjectprotein binding
dc.subjectsignal peptide
dc.subjecttranscription factor
dc.subjecttranscription factor RUNX2
dc.subjectWWTR1 protein, human
dc.subjectArticle
dc.subjectbreast cancer
dc.subjectbreast cancer cell line
dc.subjectcancer growth
dc.subjectcarcinogenicity
dc.subjectcell nucleus
dc.subjectcellular distribution
dc.subjectcontrolled study
dc.subjectdrug targeting
dc.subjectgene silencing
dc.subjecthuman
dc.subjecthuman cell
dc.subjectoverall survival
dc.subjectprotein domain
dc.subjectprotein expression
dc.subjectprotein function
dc.subjectprotein localization
dc.subjectprotein protein interaction
dc.subjectsignal transduction
dc.subject3T3 cell line
dc.subjectanimal
dc.subjectbreast tumor
dc.subjectdrug effects
dc.subjectgene expression regulation
dc.subjectgenetics
dc.subjectMCF-7 cell line
dc.subjectmetabolism
dc.subjectmouse
dc.subjectmulticellular spheroid
dc.subjectpathology
dc.subjectreverse transcription polymerase chain reaction
dc.subjectRNA interference
dc.subjectsolubility
dc.subjectWestern blotting
dc.subjectAnimals
dc.subjectBlotting, Western
dc.subjectBreast Neoplasms
dc.subjectCadherins
dc.subjectCore Binding Factor Alpha 1 Subunit
dc.subjectDoxycycline
dc.subjectGene Expression Regulation, Neoplastic
dc.subjectHumans
dc.subjectIntracellular Signaling Peptides and Proteins
dc.subjectMCF-7 Cells
dc.subjectMice
dc.subjectNIH 3T3 Cells
dc.subjectProtein Binding
dc.subjectReceptor, ErbB-2
dc.subjectReverse Transcriptase Polymerase Chain Reaction
dc.subjectRNA Interference
dc.subjectSignal Transduction
dc.subjectSolubility
dc.subjectSpheroids, Cellular
dc.subjectTranscription Factors
dc.typeArticle
dc.contributor.departmentPHYSIOLOGY
dc.description.doi10.18632/oncotarget.4654
dc.description.sourcetitleOncotarget
dc.description.volume6
dc.description.issue29
dc.description.page28132-28150
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