0000000000116440

AUTHOR

Stefano Piccolo

showing 5 related works from this author

A Mutually Stimulating Loop Involving Emx2 and Canonical Wnt Signalling Specifically Promotes Expansion of Occipital Cortex and Hippocampus

2005

The correct size of the different areas composing the mature cerebral cortex depends on the proper early allocation of cortical progenitors to their distinctive areal fates, as well as on appropriate subsequent tuning of their area-specific proliferation--differentiation profiles. Whereas much is known about the genetics of the former process, the molecular mechanisms regulating proliferation and differentiation rates within distinctive cortical proto-areas are still largely obscure. Here we show that a mutual stimulating loop, involving Emx2 and canonical Wnt signalling, specifically promotes expansion of the occipito-hippocampal anlage. Collapse of this loop occurring in Emx2 2/2 mutants …

Cognitive NeuroscienceEMX2HippocampusSettore BIO/11 - Biologia MolecolareProneural genescell cycle genesBiologyHippocampusMiceCellular and Molecular NeuroscienceCortex (anatomy)medicineAnimalsWnt signallingHomeodomain ProteinsNeuronsproneural genesStem CellsGene Expression Regulation DevelopmentalCell DifferentiationCell cycleareal sizingCell Cycle GeneMice Mutant StrainsWnt Proteinsmedicine.anatomical_structureCerebral cortexEmx2Occipital LobeOccipital lobeareal sizing; Emx2; Wnt signalling; cell cycle genes; proneural genesNeuroscienceCell DivisionSignal TransductionTranscription FactorsCerebral Cortex
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Abstract CT261: METAMECH -A Master Observational Trial empowering mechanobiology translational research and mechanobased proof of concept trials in b…

2020

Abstract Background: Breast cancer (BC) is the most frequent tumor in women worldwide. BC lethality is caused by aggressive, therapy-resistant metastases (mBC). Preliminary data have shown that mBC lesions are invariably embedded into a densely packed network of fibrous extracellular matrix, making the metastatic microenvironment a potent inducer of mechanical inputs, ultimately leading to the activation of the transcription factors YAP/TAZ. Aberrant mechano-signaling could thus represent a vulnerability of metastasis, which can be exploited to develop new therapeutic strategies. To investigate how metastatic outgrowth is regulated by the physical properties of the microenvironment, and how…

OncologyCancer Researchmedicine.medical_specialtybusiness.industryObservational TrialCancerTranslational researchmedicine.diseaseImaging dataMetastasisBreast cancerClinical researchOncologyInternal medicineMedicineSample collectionbusinessCancer Research
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YAP/TAZ activity in stromal cells prevents ageing by controlling cGAS-STING

2022

Ageing is intimately connected to the induction of cell senescence(1,2), but why this is so remains poorly understood. A key challenge isthe identification of pathways that normally suppress senescence, are lost during ageing and are functionally relevant to oppose ageing(3). Here we connected the structural and functional decline of ageing tissues to attenuated function of the master effectors of cellular mechanosignalling YAP and TAZ. YAP/TAZ activity declines during physiological ageing in stromal cells, and mimicking such decline through genetic inactivation of YAP/TAZ in these cells leads to accelerated ageing. Conversely, sustaining YAP function rejuvenates old cells and opposes the e…

AgingMechanotransductionActin-Related Protein 2; Cellular Senescence; Extracellular Matrix; Healthy Aging; Immunity Innate; Lamin Type B; Mechanotransduction Cellular; Nuclear Envelope; Signal Transduction; Aging; Membrane Proteins; Nucleotidyltransferases; Stromal Cells; Transcriptional Coactivator with PDZ-Binding Motif Proteins; YAP-Signaling ProteinsNuclear EnvelopeSettore MED/08 - Anatomia PatologicaYAP TAZ ageing C-GAS STINGMechanotransduction CellularArticleHealthy AgingInnateCellular SenescenceAdaptor Proteins Signal TransducingMultidisciplinaryLamin Type BImmunityMembrane ProteinsYAP-Signaling ProteinsPhosphoproteinsNucleotidyltransferasesImmunity InnateExtracellular MatrixTranscriptional Coactivator with PDZ-Binding Motif ProteinsActin-Related Protein 2CellularStromal CellsSignal Transduction
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TAZ is required for metastatic activity and chemoresistance of breast cancer stem cells

2015

Metastatic growth in breast cancer (BC) has been proposed as an exclusive property of cancer stem cells (CSCs). However, formal proof of their identity as cells of origin of recurrences at distant sites and the molecular events that may contribute to tumor cell dissemination and metastasis development are yet to be elucidated. In this study, we analyzed a set of patient-derived breast cancer stem cell (BCSC) lines. We found that in vitro BCSCs exhibit a higher chemoresistance and migratory potential when compared with differentiated, nontumorigenic, breast cancer cells (dBCCs). By developing an in vivo metastatic model simulating the disease of patients with early BC, we observed that BCSCs…

cancer stem cellsTAZAnimals; Biomarkers Tumor; Breast Neoplasms; Cell Line Tumor; Disease-Free Survival; Female; Gene Expression Regulation Neoplastic; Humans; Mice; Neoplasm Metastasis; Neoplasm Recurrence Local; Neoplastic Stem Cells; Transcription Factors; Xenograft Model Antitumor AssaysCancer ResearchBioinformaticschemotherapyMetastasistaz; breast cancerMiceNeoplasm Metastasiseducation.field_of_studyTumorIntracellular Signaling Peptides and ProteinsCell cycleGene Expression Regulation NeoplasticLocalNeoplastic Stem Cellsbreast cancer; cancer stem cells; chemotherapy; metastasis; TAZ; Animals; Biomarkers Tumor; Breast Neoplasms; Cell Line Tumor; Disease-Free Survival; Female; Gene Expression Regulation Neoplastic; Humans; Intracellular Signaling Peptides and Proteins; Mice; Neoplasm Metastasis; Neoplasm Recurrence Local; Neoplastic Stem Cells; Xenograft Model Antitumor Assays; Molecular Biology; Genetics; Cancer ResearchFemaleStem cellPopulationBreast NeoplasmsBiologyDisease-Free SurvivalCell Linebreast cancer cancer stem cells TAZBreast cancerbreast cancerCancer stem cellSettore MED/04 - PATOLOGIA GENERALECell Line TumormedicineBiomarkers TumorGeneticsmetastasisAnimalsHumanseducationMolecular BiologyHippo signaling pathwayNeoplasticCancermedicine.diseaseXenograft Model Antitumor AssaysNeoplasm RecurrenceGene Expression RegulationTranscriptional Coactivator with PDZ-Binding Motif ProteinsCancer researchTrans-ActivatorsNeoplasm Recurrence LocalBiomarkersTranscription Factors
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Epigenomic landscape of human colorectal cancer unveils an aberrant core of pan-cancer enhancers orchestrated by YAP/TAZ

2021

Cancer is characterized by pervasive epigenetic alterations with enhancer dysfunction orchestrating the aberrant cancer transcriptional programs and transcriptional dependencies. Here, we epigenetically characterize human colorectal cancer (CRC) using de novo chromatin state discovery on a library of different patient-derived organoids. By exploring this resource, we unveil a tumor-specific deregulated enhancerome that is cancer cell-intrinsic and independent of interpatient heterogeneity. We show that the transcriptional coactivators YAP/TAZ act as key regulators of the conserved CRC gained enhancers. The same YAP/TAZ-bound enhancers display active chromatin profiles across diverse human t…

0301 basic medicineOrganoidEpigenomicsTranscription FactorGeneral Physics and AstronomyColorectal NeoplasmAdaptor Proteins Signal Transducing; Colorectal Neoplasms; Gene Expression Regulation Neoplastic; Histone Code; Humans; Models Genetic; Organoids; RNA-Seq; Single-Cell Analysis; Trans-Activators; Transcription Factors; Tumor Cells Cultured; Enhancer Elements Genetic; Epigenesis GeneticEpigenesis Genetic0302 clinical medicineModelsAdaptor Proteins Signal Transducing Colorectal Neoplasms Gene Expression Regulation NeoplasticHistone Code Humans Models Genetic Organoids RNA-Seq Single-Cell Analysis Trans-Activators Transcription Factors Tumor Cells Cultured Enhancer Elements Genetic Epigenesis GeneticTumor Cells CulturedCancer genomicsHistone codeRNA-SeqEpigenomicsAdaptor Proteins Signal Transducing; Colorectal Neoplasms; Gene Expression Regulation Neoplastic; Histone Code; Humans; Models Genetic; Organoids; RNA-Seq; Single-Cell Analysis; Trans-Activators; Transcription Factors; Transcriptional Coactivator with PDZ-Binding Motif Proteins; Tumor Cells Cultured; YAP-Signaling Proteins; Enhancer Elements Genetic; Epigenesis GeneticMultidisciplinaryCulturedQAdaptor Proteins3. Good healthChromatinTumor CellsGene Expression Regulation NeoplasticHistone CodeOrganoidsSingle-Cell AnalysiEnhancer Elements GeneticTrans-Activator030220 oncology & carcinogenesisSingle-Cell AnalysisColorectal NeoplasmsHumanEnhancer ElementsScienceTumour heterogeneityBiologyGeneral Biochemistry Genetics and Molecular BiologyArticle03 medical and health sciencesGeneticmedicineHumansEpigeneticsEnhancerTranscription factorAdaptor Proteins Signal TransducingNeoplasticModels GeneticSignal TransducingCancerYAP-Signaling ProteinsGeneral Chemistrymedicine.diseaseColorectal cancerdigestive system diseases030104 developmental biologyGene Expression RegulationTranscriptional Coactivator with PDZ-Binding Motif ProteinsCancer cellCancer researchTrans-ActivatorsEpigenesisTranscription Factors
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