2021
Chromosomal instability and aneuploidy as causes of cancer drug resistance
Lukow DA, Sheltzer JM. Chromosomal instability and aneuploidy as causes of cancer drug resistance. Trends In Cancer 2021, 8: 43-53. PMID: 34593353, DOI: 10.1016/j.trecan.2021.09.002.Peer-Reviewed Original ResearchConceptsChromosomal instabilityGene dosage alterationsChromosome copy number changesCopy number changesCell fitnessCancer drug resistanceCellular adaptabilitySelective pressureDrug resistanceTumor evolutionNumber changesDosage alterationsRecent evidenceAneuploidyIntratumoral heterogeneityPoor patient outcomesFitnessHigh levelsUnique vulnerabilitiesResistanceChromosomal instability accelerates the evolution of resistance to anti-cancer therapies
Lukow DA, Sausville EL, Suri P, Chunduri NK, Wieland A, Leu J, Smith JC, Girish V, Kumar AA, Kendall J, Wang Z, Storchova Z, Sheltzer JM. Chromosomal instability accelerates the evolution of resistance to anti-cancer therapies. Developmental Cell 2021, 56: 2427-2439.e4. PMID: 34352222, PMCID: PMC8933054, DOI: 10.1016/j.devcel.2021.07.009.Peer-Reviewed Original ResearchConceptsChromosomal instabilityAnti-cancer therapyCancer cell fitnessAcquisition of aneuploidyChromosome loss eventsSingle-cell sequencingEvolution of resistanceDifferent culture environmentsCellular fitnessPhenotypic plasticityCIN correlatesHuman tumorsCell fitnessHuman cellsStressful environmentsResistant populationsAcquisition of resistanceRecurrent aneuploidyCancer cellsPaclitaxel-resistant cellsCulture environmentAneuploidyPaclitaxel sensitivityFitnessCells
2020
Single-Chromosomal Gains Can Function as Metastasis Suppressors and Promoters in Colon Cancer
Vasudevan A, Baruah PS, Smith JC, Wang Z, Sayles NM, Andrews P, Kendall J, Leu J, Chunduri NK, Levy D, Wigler M, Storchová Z, Sheltzer JM. Single-Chromosomal Gains Can Function as Metastasis Suppressors and Promoters in Colon Cancer. Developmental Cell 2020, 52: 413-428.e6. PMID: 32097652, PMCID: PMC7354079, DOI: 10.1016/j.devcel.2020.01.034.Peer-Reviewed Original ResearchMeSH KeywordsAneuploidyAnimalsApoptosisCell MovementCell ProliferationChromosomal InstabilityChromosomes, Human, Pair 5Colonic NeoplasmsEpithelial-Mesenchymal TransitionFemaleHumansMaleMembrane ProteinsMiceMice, NudeNeoplasm InvasivenessNucleotidyltransferasesTumor Cells, CulturedXenograft Model Antitumor AssaysConceptsSingle extra chromosomeCell state transitionsCGAS/STING signalingCell linesCopy number dataPartial epithelial-mesenchymal transitionCancer aneuploidyPhenotypic plasticityGenomic plasticitySingle chromosomeEpithelial-mesenchymal transitionMetastasis suppressorChromosomal instabilityExtra chromosomeCertain aneuploidiesDifferent aneuploidiesCancer progressionSpecific aneuploidiesChromosomal gainsChromosomesSTING signalingMetastatic behaviorTumor progressionAneuploidyUniform driver
2013
A Transcriptional and Metabolic Signature of Primary Aneuploidy Is Present in Chromosomally Unstable Cancer Cells and Informs Clinical Prognosis
Sheltzer J. A Transcriptional and Metabolic Signature of Primary Aneuploidy Is Present in Chromosomally Unstable Cancer Cells and Informs Clinical Prognosis. Cancer Research 2013, 73: 6401-6412. PMID: 24041940, PMCID: PMC3901577, DOI: 10.1158/0008-5472.can-13-0749.Peer-Reviewed Original ResearchConceptsChromosomal instabilityPrimary cellsUnstable cancer cellsAneuploid cellsSubset of genesProliferation-independent mannerHigh mitotic activityCancer cell linesAggressive diseasePoor prognosisClinical prognosisTypes of aneuploidyPrimary aneuploidyCellular stressAbnormal karyotypeTranscriptional alterationsHuman patientsTCA cycle fluxCancerMetabolic signaturesAneuploid cancersTranscriptional signatureCancer cellsCancer linesMitotic activity
2011
The aneuploidy paradox: costs and benefits of an incorrect karyotype
Sheltzer J, Amon A. The aneuploidy paradox: costs and benefits of an incorrect karyotype. Trends In Genetics 2011, 27: 446-453. PMID: 21872963, PMCID: PMC3197822, DOI: 10.1016/j.tig.2011.07.003.Peer-Reviewed Original ResearchConceptsCell proliferationRole of aneuploidyHallmarks of cancerExperimental evolutionEnhanced proliferative capacityCellular phenotypesChromosomal instabilityAneuploid cellsNormal cellsKaryotypic imbalancesProliferative capacityAneuploidyDiverse effectsProliferationCellsPhenotypeMicroorganismsKaryotypeHallmark