2023
A PERK-Specific Inhibitor Blocks Metastatic Progression by Limiting Integrated Stress Response-Dependent Survival of Quiescent Cancer Cells.
Calvo V, Zheng W, Adam-Artigues A, Staschke K, Huang X, Cheung J, Nobre A, Fujisawa S, Liu D, Fumagalli M, Surguladze D, Stokes M, Nowacek A, Mulvihill M, Farias E, Aguirre-Ghiso J. A PERK-Specific Inhibitor Blocks Metastatic Progression by Limiting Integrated Stress Response-Dependent Survival of Quiescent Cancer Cells. Clinical Cancer Research 2023, 29: 5155-5172. PMID: 37982738, PMCID: PMC10842363, DOI: 10.1158/1078-0432.ccr-23-1427.Peer-Reviewed Original ResearchCancer cellsIntegrated stress responsePERK inhibitionRounds of therapyPERK inhibitorDormant cancer cellsQuiescent cancer cellsMicro-metastatic lesionsAnti-proliferative therapiesMetastasis biopsiesMetastatic burdenCDK4/6 inhibitorsPDX modelsSingle-cell gene expression profilingHER2 activityMetastatic progressionGene expression profilingSurvival factorUnresolved ER stressHigh expressionMouse syngeneicER stressMetastasisHER2Therapy5-Azacytidine- and retinoic-acid-induced reprogramming of DCCs into dormancy suppresses metastasis via restored TGF-β-SMAD4 signaling
Singh D, Carcamo S, Farias E, Hasson D, Zheng W, Sun D, Huang X, Cheung J, Nobre A, Kale N, Sosa M, Bernstein E, Aguirre-Ghiso J. 5-Azacytidine- and retinoic-acid-induced reprogramming of DCCs into dormancy suppresses metastasis via restored TGF-β-SMAD4 signaling. Cell Reports 2023, 42: 112560. PMID: 37267946, PMCID: PMC10592471, DOI: 10.1016/j.celrep.2023.112560.Peer-Reviewed Original ResearchConceptsDisseminated cancer cellsCancer cellsDNA methylation inhibitorNon-proliferative stateAnti-proliferative functionTranscriptional reprogrammingChromatin remodelingRetinoic acid receptorsTranscriptional programsMethylation inhibitorGrowth factor βMicroenvironmental signalsSMAD4 knockdownBreast cancer cellsDormancySuppress metastasisRARα-specific agonistLung metastasis formationNeck squamous cell carcinomaReprogrammingRetinoic acidSquamous cell carcinomaTrans retinoic acidFactor βMetastasis formation
2017
Phenotypic heterogeneity of disseminated tumour cells is preset by primary tumour hypoxic microenvironments
Fluegen G, Avivar-Valderas A, Wang Y, Padgen MR, Williams JK, Nobre A, Calvo V, Cheung JF, Bravo-Cordero JJ, Entenberg D, Castracane J, Verkhusha V, Keely PJ, Condeelis J, Aguirre-Ghiso JA. Phenotypic heterogeneity of disseminated tumour cells is preset by primary tumour hypoxic microenvironments. Nature Cell Biology 2017, 19: 120-132. PMID: 28114271, PMCID: PMC5342902, DOI: 10.1038/ncb3465.Peer-Reviewed Original ResearchConceptsBreast cancer cellsDormant DTCsTumor hypoxic microenvironmentTumor cellsHypoxic microenvironmentCancer cellsDisseminated tumor cellsPrimary tumor microenvironmentDisease relapsePoor prognosisTarget organsP27 inductionTransgenic miceSolid tumorsTumor microenvironmentHypoxia genesHypoxiaPhenotypic heterogeneityMicroenvironmentCellsChemotherapyRelapseHNSCCPrognosisTherapy