2014
Synergistic tumor suppression by combined inhibition of telomerase and CDKN1A
Gupta R, Dong Y, Solomon PD, Wettersten HI, Cheng CJ, Min JN, Henson J, Dogra SK, Hwang SH, Hammock BD, Zhu LJ, Reddel RR, Saltzman WM, Weiss RH, Chang S, Green MR, Wajapeyee N. Synergistic tumor suppression by combined inhibition of telomerase and CDKN1A. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: e3062-e3071. PMID: 25024194, PMCID: PMC4121806, DOI: 10.1073/pnas.1411370111.Peer-Reviewed Original ResearchConceptsP53-mediated transcriptional activationCyclin-dependent kinase inhibitor 1AMutant p53Telomerase inhibitionTumor suppressor p53Transcriptional activationSynergistic tumor suppressionTelomere dysfunctionCheckpoint proteinsP53 upregulated modulatorTumor suppressionCDK inhibitorsSuppressor p53Inhibitor 1AP53 activityTelomeraseHuman cancersCancer cell linesApoptosis inductionPharmacological inhibitionApoptosisCell linesPharmacological restorationP21Growth inhibition
2008
Telomere dysfunction and tumour suppression: the senescence connection
Deng Y, Chan SS, Chang S. Telomere dysfunction and tumour suppression: the senescence connection. Nature Reviews Cancer 2008, 8: 450-458. PMID: 18500246, PMCID: PMC3688269, DOI: 10.1038/nrc2393.Peer-Reviewed Original ResearchConceptsTelomere dysfunctionDysfunctional telomeresDNA damage responseKey PointsTelomeresEukaryotic chromosomesGenome instabilityShelterin complexApoptotic programDamage responseRepetitive sequencesCellular senescenceTelomeric endTumor suppressionProtein resultsP53 pathwayMutant p53TelomeresSpontaneous tumorigenesisSenescenceTumorigenesisMouse modelChromosomesDysfunctionProteinApoptosis
2007
Telomere dysfunction suppresses spontaneous tumorigenesis in vivo by initiating p53‐dependent cellular senescence
Cosme-Blanco W, Shen MF, Lazar AJ, Pathak S, Lozano G, Multani AS, Chang S. Telomere dysfunction suppresses spontaneous tumorigenesis in vivo by initiating p53‐dependent cellular senescence. EMBO Reports 2007, 8: 497-503. PMID: 17396137, PMCID: PMC1866197, DOI: 10.1038/sj.embor.7400937.Peer-Reviewed Original ResearchConceptsP53-dependent cellular senescenceSpontaneous tumorigenesisCellular senescenceCellular senescence pathwaysSenescence pathwaysCell cycle arrestSkin carcinomasSenescence markersTumorigenesisMiceDysfunctional telomeresTumor suppressionTelomere dysfunctionP53ApoptosisVivoSuppressionCarcinomaDysfunctionPathwaySenescence
2006
GCN5 Functions in Telomere Maintenance and Neural Development
Dent S, Evrard Y, Lin W, Bu P, Phan H, Chang S, Multani A. GCN5 Functions in Telomere Maintenance and Neural Development. The FASEB Journal 2006, 20: a1472-a1472. DOI: 10.1096/fasebj.20.5.a1472-e.Peer-Reviewed Original ResearchMutant embryosNeural developmentTelomere maintenanceDouble mutant embryosCatalytic site mutationsNeural tube closureGcn5 functionsTelomere defectsTelomere fusionEmbryonic lethalityHypomorphic alleleProper expressionGCN5Tube closureSite mutationSimilar defectsEnd associationEmbryosFirst evidenceApoptosisBrain developmentP53CellsTelomeresGenes
2003
Chromosome stability, in the absence of apoptosis, is critical for suppression of tumorigenesis in Trp53 mutant mice
Liu G, Parant J, Lang G, Chau P, Chavez-Reyes A, El-Naggar A, Multani A, Chang S, Lozano G. Chromosome stability, in the absence of apoptosis, is critical for suppression of tumorigenesis in Trp53 mutant mice. Nature Genetics 2003, 36: 63-68. PMID: 14702042, DOI: 10.1038/ng1282.Peer-Reviewed Original ResearchConceptsTrp53-null miceCell cycle arrestEarly onsetCycle arrestPartial cell cycle arrestMonths of ageTrp53 mutant miceSpontaneous tumorsSpontaneous tumorigenesisRare mutant formMutant miceThymic lymphomasMiceHuman tumorsSuppression of tumorigenesisTumorsAbsence of apoptosisP53 proteinP53-dependent apoptosisInduces ApoptosisLymphomaApoptosisTumorigenesisTumor suppressorP53-induced apoptosis