2023
5-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
2021
Bone marrow NG2+/Nestin+ mesenchymal stem cells drive DTC dormancy via TGF-β2
Nobre A, Risson E, Singh D, Di Martino J, Cheung J, Wang J, Johnson J, Russnes H, Bravo-Cordero J, Birbrair A, Naume B, Azhar M, Frenette P, Aguirre-Ghiso J. Bone marrow NG2+/Nestin+ mesenchymal stem cells drive DTC dormancy via TGF-β2. Nature Cancer 2021, 2: 327-339. PMID: 34993493, PMCID: PMC8730384, DOI: 10.1038/s43018-021-00179-8.Peer-Reviewed Original ResearchMeSH KeywordsBone MarrowBreast NeoplasmsFemaleHumansMesenchymal Stem CellsNeoplasm Recurrence, LocalNestinTumor MicroenvironmentConceptsMesenchymal stem cellsDTC dormancyHematopoietic stem cell quiescenceStem cellsStem cell quiescenceBone morphogenetic proteinTGF-β2Niche homeostasisMorphogenetic proteinsCell quiescenceBone marrow microenvironmentGenetic depletionP27 inductionDormancyConditional knockoutMarrow microenvironmentMetastatic outgrowthEstrogen receptor-positive BCExtrinsic factorsGrowth factorCellsTumor cellsBone relapseSystemic recurrenceBreast cancer
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