16 results on '"Cicatiello, A. G."'
Search Results
2. Removal of model bacterial bioaerosol in a lab-scale electrostatic precipitator
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La Motta, F., de Falco, G., Colicchio, R., Salvatore, P., Cicatiello, A. G., Pagliuca, C., Di Natale, F., CAROTENUTO, Claudia, E. Bolzacchini, La Motta, F., de Falco, G., Colicchio, R., Salvatore, P., Cicatiello, A. G., Pagliuca, C., Carotenuto, Claudia, and Di Natale, F.
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- 2015
3. Metabolic Effects of the Intracellular Regulation of Thyroid Hormone: Old Players, New Concepts
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Cicatiello, Annunziata G., primary, Di Girolamo, Daniela, additional, and Dentice, Monica, additional
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- 2018
- Full Text
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4. Novel Approach for Evaluation of Bacteroides fragilis Protective Role against Bartonella henselae Liver Damage in Immunocompromised Murine Model
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Pagliuca, Chiara, primary, Cicatiello, Annunziata G., additional, Colicchio, Roberta, additional, Greco, Adelaide, additional, Cerciello, Raimondo, additional, Auletta, Luigi, additional, Albanese, Sandra, additional, Scaglione, Elena, additional, Pagliarulo, Caterina, additional, Pastore, Gabiria, additional, Mansueto, Gelsomina, additional, Brunetti, Arturo, additional, Avallone, Bice, additional, and Salvatore, Paola, additional
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- 2016
- Full Text
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5. Identification of Inquilinus limosus in cystic fibrosis: A first report in Italy
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Cicatiello, A. G., Iula, D. V., Pagliuca, C., Pastore, G., Pagliarulo, C., Catania, M. R., Colicchio, R., Picardi, M., Raia, V., Paola SALVATORE, Cicatiello, ANNUNZIATA GAETANA, Iula, VITA DORA, Pagliuca, Chiara, Gabiria, Pastore, Caterina, Pagliarulo, Catania, MARIA ROSARIA, Colicchio, Roberta, Picardi, Marco, Raia, Valeria, and Salvatore, Paola
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Inquilinus limosu ,Cystic fibrosi ,Mucoid strain identification - Abstract
Cystic fibrosis is a genetic disorder associated with a polymicrobial lung infection where classical pathogens and newly identified bacteria may interact. Inquilinus limosus is an a-proteobacterium recently isolated in the airways of cystic fibrosis patient. We report the first case in Italy of I.limosus isolation from the sputum sample of a cystic fibrosis patient. The patient is a 20-years-old man with cystic fibrosis, regularly attending the Regional Care Center for Cystic Fibrosis at the Federico II University Hospital of Naples. Microbiological culture methods detected a mucoid gram negative bacillus in the patient???s sputum sample. The isolate exhibited a distinct antimicrobial susceptibility profile with a high MIC for several drugs. The MALDI-TOF mass spectrometry analysis indicated the bacterium isolated as I. limosus, confirmed by 16s rDNA sequence analysis. The described clinical case demonstrates how the bacterial biodiversity in the airways of cystic fibrosis patients is still underestimated. Cystic fibrosis lung represents an ecological niche suitable for growth of a wide variety of unusual bacteria not commonly associated with human diseases, such as I. limosus. Therefore further studies are needed to evaluate the epidemiology and clinical implications of I. limosus in the physiopathology of cystic fibrosis lung infection.
6. Genotyping of Toxoplasma gondii strain directly from human CSF samples of congenital toxoplasmosis clinical case
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Pagliuca, C., Pastore, G., Scaglione, E., Migliucci, A., Maruotti, G. M., Cicatiello, A. G., Elena SALVATORE, Picardi, M., Sammartino, J. C., Buonocore, M. C., Martinelli, P., Iaccarino, E., Colicchio, R., Salvatore, P., Pagliuca, Chiara, Pastore, G, Scaglione, Elena, Migliucci, A, Maruotti, GIUSEPPE MARIA, Cicatiello, ANNUNZIATA GAETANA, Salvatore, Elena, Picardi, Marco, Camilla Sammartino, J, Consiglio Buonocore, M, Martinelli, Pasquale, Iaccarino, E, Colicchio, Roberta, and Salvatore, Paola
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Genotyping ,Congenital toxoplasmosi ,Nested-PCR-RFLP ,Toxoplasma gondii - Abstract
This report describes a case of congenital toxoplasmosis in a newborn in Southern Italy. A pregnant mother had been admitted at the 20th week of her pregnancy on account of pharyngodynia and laterocervical lymphadenopathy. Although serological testing of the mother's serum documented a seroconversion with positive IgG and IgM anti-Toxoplasma antibodies during II trimester, the woman refused to perform prenatal diagnosis for congenital toxoplasmosis. Fetal ultrasound scan already showed mild asymmetrical triventricular hydrocephaly and cerebral calcifications. After birth, real-time PCR on cerebrospinal fluid and blood samples of the newborn showed a positive result for 529bp-repeat element DNA of T. gondii, In addition brain magnetic resonance imaging and computed tomography showed a characteristic diffuse brain tissue loss associated with hydrocephalus. For the first time molecular characterization of T. gondii isolate was performed directly from the newborn's CSF samples by using nested-PCR-RFLP of sag-2 and pk1 genes. The PCR-RLFP analysis revealed that the isolate belongs to the clonal type II, the predominant lineage causing human toxoplasmosis, as confirmed by DNA sequencing.
7. A Type 2 Deiodinase-Dependent Increase in Vegfa Mediates Myoblast-Endothelial Cell Crosstalk During Skeletal Muscle Regeneration
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Simone Magagnin Wajner, Monica Dentice, Cristina Luongo, Annunziata Gaetana Cicatiello, Raffaele Ambrosio, Diane E. Handy, P. Reed Larsen, Ashley N. Ogawa-Wong, Colleen Carmody, Domenico Salvatore, Xingxing An, Ann Marie Zavacki, An, X., Ogawa-Wong, A., Carmody, C., Ambrosio, R., Cicatiello, A. G., Luongo, C., Salvatore, D., Handy, D. E., Larsen, P. R., Wajner, S. M., Dentice, M., and Zavacki, A. M.
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deiodinase ,Male ,Vascular Endothelial Growth Factor A ,Myoblasts, Skeletal ,Endocrinology, Diabetes and Metabolism ,Human Umbilical Vein Endothelial Cell ,Deiodinase ,Neovascularization, Physiologic ,DIO2 ,030209 endocrinology & metabolism ,Muscle Development ,Iodide Peroxidase ,Cell Line ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Cell Movement ,satellite cell ,Paracrine Communication ,medicine ,Regeneration ,Myocyte ,skeletal muscle ,Muscle, Skeletal ,Cell Proliferation ,Mice, Knockout ,biology ,Animal ,Chemistry ,angiogenesi ,Skeletal muscle ,thyroid hormone ,VEGF ,Up-Regulation ,Cell biology ,Mice, Inbred C57BL ,Endothelial stem cell ,Vascular endothelial growth factor A ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,biology.protein ,Stem cell ,Intracellular ,Human ,Signal Transduction - Abstract
Background: The type 2 deiodinase (DIO2) converts thyroxine to 3,3′,5-triiodothyronine (T3), modulating intracellular T3. An increase in DIO2 within muscle stem cells during skeletal muscle regeneration leads to T3-dependent potentiation of differentiation. The muscle stem cell niche comprises numerous cell types, which coordinate the regeneration process. For example, muscle stem cells provide secretory signals stimulating endothelial cell-mediated vascular repair, and, in turn, endothelial cells promote muscle stem differentiation. We hypothesized that Dio2 loss in muscle stem cells directly impairs muscle stem cell-endothelial cell communication, leading to downstream disruption of endothelial cell function. Methods: We assessed the production of proangiogenic factors in differentiated C2C12 cells and in a C2C12 cell line without Dio2 (D2KO C2C12) by real-time quantitative-polymerase chain reaction and enzyme-linked immunosorbent assay. Conditioned medium (CM) was collected daily in parallel to evaluate its effects on human umbilical vein endothelial cell (HUVEC) proliferation, migration and chemotaxis, and vascular network formation. The effects of T3-treatment on vascular endothelial growth factor (Vegfa) mRNA expression in C2C12 cells and mouse muscle were assessed. Chromatin immunoprecipitation (ChIP) identified thyroid hormone receptor (TR) binding to the Vegfa gene. Using mice with a targeted disruption of Dio2 (D2KO mice), we determined endothelial cell number by immunohistochemistry/flow cytometry and evaluated related gene expression in both uninjured and injured skeletal muscle. Results: In differentiated D2KO C2C12 cells, Vegfa expression was 46% of wildtype (WT) C2C12 cells, while secreted VEGF was 45%. D2KO C2C12 CM exhibited significantly less proangiogenic effects on HUVECs. In vitro and in vivo T3 treatment of C2C12 cells and WT mice, and ChIP using antibodies against TRα, indicated that Vegfa is a direct genomic T3 target. In uninjured D2KO soleus muscle, Vegfa expression was decreased by 28% compared with WT mice, while endothelial cell numbers were decreased by 48%. Seven days after skeletal muscle injury, D2KO mice had 36% fewer endothelial cells, coinciding with an 83% decrease in Vegfa expression in fluorescence-activated cell sorting purified muscle stem cells. Conclusion: Dio2 loss in the muscle stem cell impairs muscle stem cell-endothelial cell crosstalk via changes in the T3-responsive gene Vegfa, leading to downstream impairment of endothelial cell function both in vitro and in vivo.
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- 2021
8. Thyroid hormone regulates glutamine metabolism and anaplerotic fluxes by inducing mitochondrial glutamate aminotransferase GPT2
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Annunziata Gaetana Cicatiello, Serena Sagliocchi, Annarita Nappi, Emery Di Cicco, Caterina Miro, Melania Murolo, Mariano Stornaiuolo, Monica Dentice, Cicatiello, Annunziata Gaetana, Sagliocchi, Serena, Nappi, Annarita, Di Cicco, Emery, Miro, Caterina, Murolo, Melania, Stornaiuolo, Mariano, Dentice, Monica, Cicatiello, A. G., Sagliocchi, S., Nappi, A., Di Cicco, E., Miro, C., Murolo, M., Stornaiuolo, M., and Dentice, M.
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Thyroid Hormones ,GPT2 ,Glutamine ,Intellectual Disability ,glutamine metabolism ,Humans ,Alanine Transaminase ,skeletal muscle ,thyroid hormone ,type 2 deiodinase ,General Biochemistry, Genetics and Molecular Biology ,Transaminases - Abstract
Thyroid hormones (THs) are key metabolic regulators coordinating short- and long-term energy needs. In skeletal muscle, THs modulate energy metabolism in pathophysiological conditions. Indeed, hypo- and hyperthyroidism are leading causes of muscle weakness and strength; however, the metabolic pathways underlying these effects are still poorly understood. Using molecular, biochemical, and isotope-tracing approaches combined with mass spectrometry and denervation experiments, we find that THs regulate glutamine metabolism and anaplerotic fluxes by up-regulating the glutamate pyruvate transaminase 2 (GPT2) gene. In humans, GPT2 autosomal recessive mutations cause a neurological syndrome characterized by intellectual disability, microcephaly, and progressive motor symptoms. Here, we demonstrate a role of the TH/GPT2 axis in skeletal muscle in which it regulates muscle weight and fiber diameter in resting and atrophic conditions and results in protection from muscle loss during atrophy. These results describe an anabolic route by which THs rewire glutamine metabolism toward the maintenance of muscle mass.
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- 2021
9. Thyroid hormone and androgen signals mutually interplay and enhance inflammation and tumorigenic activation of tumor microenvironment in prostate cancer
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Caterina Miro, Angelo Di Giovanni, Melania Murolo, Annunziata Gaetana Cicatiello, Annarita Nappi, Serena Sagliocchi, Emery Di Cicco, Francesco Morra, Angela Celetti, Francesco Pacifico, Ciro Imbimbo, Felice Crocetto, Monica Dentice, Miro, C., Di Giovanni, A., Murolo, M., Cicatiello, A. G., Nappi, A., Sagliocchi, S., Di Cicco, E., Morra, F., Celetti, A., Pacifico, F., Imbimbo, C., Crocetto, F., and Dentice, M.
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Inflammation ,Male ,Cancer Research ,Thyroid Hormones ,Prostate cancer ,Carcinogenesis ,Prostatic Hyperplasia ,Prostatic Neoplasms ,Oncology ,Receptors, Androgen ,Cell Line, Tumor ,Deiodinase ,Androgens ,Tumor Microenvironment ,Humans - Abstract
Prostate Cancer (PCa) is the most commonly diagnosed non-cutaneous cancer in males and the fifth leading cause of death worldwide. The majority of PCas are androgen-sensitive, with a significant up-regulation of Androgen Receptor (AR) that causes a stimulatory effect on growth and progression of cancer cells. For this reason, the first-line therapy for PCa is androgen ablation, even if it ultimately fails due to the onset of hormone-refractory state, in which the malignant cells do not sense the androgen signal anymore. Besides androgens, a growing number of evidence suggests that Thyroid Hormones (THs) mediate tumor-promoting effects in a variety of human cancers, as Epithelial-to-Mesenchymal Transition (EMT), invasion and metastasis and also stimulation of angiogenesis and tumor metabolism. Moreover, epidemiological studies demonstrated an increased risk for PCa in patients with lower levels of Thyreotropin (TSH). Here, we investigated if intracellular TH metabolism affects Benign Prostatic Hyperplasia (BPH) and PCa formation and progression. We found that the intracellular TH metabolism is a crucial determinant of PCa behavior. We observed that a dynamic stage-specific expression of the THs modulating enzymes, the deiodinases, is required for the progression of BPH to PCa malignancy. By acting simultaneously on epithelial cancer cells and fibroblasts, THs exert a proliferative and pro-inflammatory effect cooperating with androgens. These findings suggest that androgens and THs may interplay and mediate a coordinate effect on human PCa formation and progression. In light of our results, future perspective could be to explore the potential benefits of THs intracellular modulators aimed to counteract PCa progression.
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- 2021
10. Selective Inhibition of Genomic and Non-Genomic Effects of Thyroid Hormone Regulates Muscle Cell Differentiation and Metabolic Behavior
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Caterina Miro, Mariano Stornaiuolo, Maddalena Raia, Annunziata Gaetana Cicatiello, Emery Di Cicco, Monica Dentice, Annarita Nappi, Melania Murolo, Serena Sagliocchi, Lucia D’Esposito, Rossella Di Paola, Nappi, A., Murolo, M., Sagliocchi, S., Miro, C., Cicatiello, A. G., Di Cicco, E., Di Paola, R., Raia, M., D'Esposito, L., Stornaiuolo, M., and Dentice, M.
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0301 basic medicine ,deiodinase ,Myoblast proliferation ,Thyroid Hormones ,QH301-705.5 ,Deiodinase ,DIO2 ,Muscle Cell ,030209 endocrinology & metabolism ,Iodide Peroxidase ,Catalysis ,Article ,Inorganic Chemistry ,03 medical and health sciences ,Mice ,0302 clinical medicine ,genomic and non-genomic action ,medicine ,Gene silencing ,Myocyte ,Animals ,Biology (General) ,Physical and Theoretical Chemistry ,Muscle, Skeletal ,QD1-999 ,Molecular Biology ,Spectroscopy ,Muscle Cells ,biology ,Muscle cell differentiation ,Animal ,Organic Chemistry ,Integrin beta3 ,Skeletal muscle ,Cell Differentiation ,General Medicine ,thyroid hormone ,Computer Science Applications ,Cell biology ,Chemistry ,030104 developmental biology ,medicine.anatomical_structure ,Nuclear receptor ,biology.protein - Abstract
Thyroid hormones (THs) are key regulators of different biological processes. Their action involves genomic and non-genomic mechanisms, which together mediate the final effects of TH in target tissues. However, the proportion of the two processes and their contribution to the TH-mediated effects are still poorly understood. Skeletal muscle is a classical target tissue for TH, which regulates muscle strength and contraction, as well as energetic metabolism of myofibers. Here we address the different contribution of genomic and non-genomic action of TH in skeletal muscle cells by specifically silencing the deiodinase Dio2 or the β3-Integrin expression via CRISPR/Cas9 technology. We found that myoblast proliferation is inversely regulated by integrin signal and the D2-dependent TH activation. Similarly, inhibition of the nuclear receptor action reduced myoblast proliferation, confirming that genomic action of TH attenuates proliferative rates. Contrarily, genomic and non-genomic signals promote muscle differentiation and the regulation of the redox state. Taken together, our data reveal that integration of genomic and non-genomic signal pathways finely regulates skeletal muscle physiology. These findings not only contribute to the understanding of the mechanisms involved in TH modulation of muscle physiology but also add insight into the interplay between different mechanisms of action of TH in muscle cells.
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- 2021
11. Thyroid Hormone Enhances Angiogenesis and the Warburg Effect in Squamous Cell Carcinomas
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Melania Murolo, Serena Sagliocchi, Domenico Salvatore, Mariano Stornaiuolo, Sandra Albanese, Ann Marie Zavacki, Emery Di Cicco, Sara Amiranda, Marcello Mancini, Caterina Miro, Annarita Nappi, Annunziata Gaetana Cicatiello, Valentina Belli, Monica Dentice, Teresa Troiani, Miro, C., Nappi, A., Cicatiello, A. G., Di Cicco, E., Sagliocchi, S., Murolo, M., Belli, V., Troiani, T., Albanese, S., Amiranda, S., Zavacki, A. M., Stornaiuolo, M., Mancini, M., Salvatore, D., and Dentice, M.
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0301 basic medicine ,squamous cell carcinoma ,Cancer Research ,Cell type ,Angiogenesis ,Cell ,Biology ,Article ,03 medical and health sciences ,angiogenesis ,0302 clinical medicine ,Deiodinase ,medicine ,Glycolysis ,RC254-282 ,thyroid hormones ,Cancer ,deiodinases ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Warburg effect ,Angiogenesi ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Cancer cell ,Cancer research ,Hormone - Abstract
Simple Summary Cancer cells rewire their metabolism to promote growth, survival, proliferation, and long-term maintenance. Aerobic glycolysis is a prominent trait of many cancers; contextually, glutamine addiction, enhanced glucose uptake and aerobic glycolysis sustain the metabolic needs of rapidly proliferating cancer cells. Thyroid hormone (TH) is a positive regulator of tumor progression and metastatic conversion of squamous cell carcinoma (SCC). Accordingly, overexpression of the TH activating enzyme, D2, is associated with metastatic SCC. The aim of our study was to assess the ability of TH and its activating enzyme in promoting key tracts of cancer progression such as angiogenesis, response to hypoxia and metabolic adaptation. By performing in vivo and in vitro studies, we demonstrate that TH induces VEGF-A in cancer cells and fosters aerobic glycolysis inducing pro-glycolytic mediators, thus implying that TH signal attenuation represents a therapeutic tool to contrast tumor angiogenesis and tumor progression. Abstract Cancer angiogenesis is required to support energetic demand and metabolic stress, particularly during conditions of hypoxia. Coupled to neo-vasculogenesis, cancer cells rewire metabolic programs to sustain growth, survival and long-term maintenance. Thyroid hormone (TH) signaling regulates growth and differentiation in a variety of cell types and tissues, thus modulating hyper proliferative processes such as cancer. Herein, we report that TH coordinates a global program of metabolic reprogramming and induces angiogenesis through up-regulation of the VEGF-A gene, which results in the enhanced proliferation of tumor endothelial cells. In vivo conditional depletion of the TH activating enzyme in a mouse model of cutaneous squamous cell carcinoma (SCC) reduces the concentration of TH in the tumoral cells and results in impaired VEGF-A production and attenuated angiogenesis. In addition, we found that TH induces the expression of the glycolytic genes and fosters lactate production, which are key traits of the Warburg effect. Taken together, our results reveal a TH–VEGF-A–HIF1α regulatory axis leading to enhanced angiogenesis and glycolytic flux, which may represent a target for SCC therapy.
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- 2021
12. The NANOG Transcription Factor Induces Type 2 Deiodinase Expression and Regulates the Intracellular Activation of Thyroid Hormone in Keratinocyte Carcinomas
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Serena Sagliocchi, Tommaso Porcelli, Annarita Nappi, Mariano Stornaiuolo, Caterina Miro, Daniela Di Girolamo, Cristina Luongo, Maria Angela De Stefano, Monica Dentice, Emery Di Cicco, Annunziata Gaetana Cicatiello, Raffaele Ambrosio, Giuseppina Mancino, Nappi, A., Di Cicco, E., Miro, C., Cicatiello, A. G., Sagliocchi, S., Mancino, G., Ambrosio, R., Luongo, C., Di Girolamo, D., De Stefano, M. A., Porcelli, T., Stornaiuolo, M., and Dentice, M.
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0301 basic medicine ,Homeobox protein NANOG ,Cancer Research ,Deiodinase ,Biology ,medicine.disease_cause ,lcsh:RC254-282 ,Article ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Transcription factor ,skin cancer ,Activator (genetics) ,Thyroid ,deiodinases ,Cell migration ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,thyroid hormone ,3. Good health ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,Carcinogenesis ,Hormone - Abstract
Type 2 deiodinase (D2), the principal activator of thyroid hormone (TH) signaling in target tissues, is expressed in cutaneous squamous cell carcinomas (SCCs) during late tumorigenesis, and its repression attenuates the invasiveness and metastatic spread of SCC. Although D2 plays multiple roles in cancer progression, nothing is known about the mechanisms regulating D2 in cancer. To address this issue, we investigated putative upstream regulators of D2 in keratinocyte carcinomas. We found that the expression of D2 in SCC cells is positively regulated by the NANOG transcription factor, whose expression, besides being causally linked to embryonic stemness, is associated with many human cancers. We also found that NANOG binds to the D2 promoter and enhances D2 transcription. Notably, blockage of D2 activity reduced NANOG-induced cell migration as well as the expression of key genes involved in epithelial&ndash, mesenchymal transition in SCC cells. In conclusion, our study reveals a link among endogenous endocrine regulators of cancer, thyroid hormone and its activating enzyme, and the NANOG regulator of cancer biology. These findings could provide the basis for the development of TH inhibitors as context-dependent anti-tumor agents.
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- 2020
13. Author Correction: Thyroid hormone induces progression and invasiveness of squamous cell carcinomas by promoting a ZEB-1/E-cadherin switch (Nature Communications, (2019), 10, 1, (5410), 10.1038/s41467-019-13140-2)
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Miro, Caterina, di Cicco, Emery, Ambrosio, Raffaele, Mancino, Giuseppina, di Girolamo, Daniela, Cicatiello, Annunziata Gaetana, Sagliocchi, Serena, Nappi, Annarita, de Stefano, Maria Angela, Luongo, Cristina, Antonini, Dario, Visconte, Feliciano, Varricchio, Silvia, Ilardi, Gennaro, del Vecchio, Luigi, Staibano, Stefania, Boelen, Anita, Blanpain, Cedric, Missero, Caterina, Salvatore, Domenico, Dentice, Monica, Miro, C., Di Cicco, E., Ambrosio, R., Mancino, G., Di Girolamo, D., Cicatiello, A. G., Sagliocchi, S., Nappi, A., De Stefano, M. A., Luongo, C., Antonini, D., Visconte, F., Varricchio, S., Ilardi, G., Del Vecchio, L., Staibano, S., Boelen, A., Blanpain, C., Missero, C., Salvatore, D., Dentice, M., Laboratory for Endocrinology, and AGEM - Endocrinology, metabolism and nutrition
- Abstract
The original version of this Article contained an error in the author affiliations. Silvia Varricchio, Gennaro Ilardi and Stefania Staibanow were incorrectly associated with ‘Department of Public Health, University of Naples "Federico II", Naples, Italy’ instead of the correct ‘Department of Advanced Biomedical Sciences, University of Naples “Federico II”, Naples, Italy.’ This has now been corrected in both the PDF and HTML versions of the Article.
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- 2020
14. The Thyroid Hormone Inactivator Enzyme, Type 3 Deiodinase, Is Essential for Coordination of Keratinocyte Growth and Differentiation
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Emery Di Cicco, Mariano Stornaiuolo, Cristina Luongo, Pietro Formisano, Giuseppina Mancino, Daniela Di Girolamo, Caterina Miro, Federica Saracino, Maria Angela De Stefano, Tommaso Porcelli, Monica Dentice, Annarita Sibilio, Annarita Nappi, Giuseppe Perruolo, Melania Murolo, Serena Sagliocchi, Annunziata Gaetana Cicatiello, Raffaele Ambrosio, Mancino, G., Sibilio, A., Luongo, C., Di Cicco, E., Miro, C., Cicatiello, A. G., Nappi, A., Sagliocchi, S., Ambrosio, R., De Stefano, M. A., Di Girolamo, D., Porcelli, T., Murolo, M., Saracino, F., Perruolo, G., Formisano, P., Stornaiuolo, M., and Dentice, M.
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Keratinocytes ,deiodinase ,Thyroid Hormones ,Endocrinology, Diabetes and Metabolism ,Deiodinase ,030209 endocrinology & metabolism ,Context (language use) ,Biology ,Iodide Peroxidase ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Endocrinology ,medicine ,Animals ,Homeostasis ,Mice, Knockout ,Triiodothyronine ,integumentary system ,Epidermis (botany) ,deiodinases ,Cell Differentiation ,skin homeostasi ,Hair follicle ,thyroid hormone ,Cell biology ,medicine.anatomical_structure ,skin homeostasis ,030220 oncology & carcinogenesis ,biology.protein ,Epidermis ,Keratinocyte ,Hormone - Abstract
Background: Thyroid hormones (THs) are key regulators of development, tissue differentiation, and maintenance of metabolic balance in virtually every cell of the body. Accordingly, severe alteration of TH action during fetal life leads to permanent deficits in humans. The skin is among the few adult tissues expressing the oncofetal protein type 3 deiodinase (D3), the TH inactivating enzyme. Here, we demonstrate that D3 is dynamically regulated during epidermal ontogenesis. Methods: To investigate the function of D3 in a postdevelopmental context, we used a mouse model of conditional epidermal-specific D3 depletion. Loss of D3 resulted in tissue hypoplasia and enhanced epidermal differentiation in a cell-autonomous manner. Results: Accordingly, wound healing repair and hair follicle cycle were altered in the D3-depleted epidermis. Further, in vitro ablation of D3 in primary culture of keratinocytes indicated that various markers of stratified epithelial layers were upregulated, thereby confirming the pro-differentiative action of D3 depletion and the consequent increased intracellular triiodothyronine levels. Notably, loss of D3 reduced the clearance of systemic TH in vivo, thereby demonstrating the critical requirement for epidermal D3 in the maintenance of TH homeostasis. Conclusion: In conclusion, our results show that the D3 enzyme is a key TH-signaling component in the skin, thereby providing a striking example of a physiological context for deiodinase-mediated TH metabolism, as well as a rationale for therapeutic manipulation of deiodinases in pathophysiological contexts.
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- 2020
15. Thyroid hormone induces progression and invasiveness of squamous cell carcinomas by promoting a ZEB-1/E-cadherin switch
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Serena Sagliocchi, Cédric Blanpain, Gennaro Ilardi, Silvia Varricchio, Caterina Missero, Anita Boelen, Caterina Miro, Stefania Staibano, Daniela Di Girolamo, Annunziata Gaetana Cicatiello, Raffaele Ambrosio, Dario Antonini, Annarita Nappi, Feliciano Visconte, Cristina Luongo, Emery Di Cicco, Domenico Salvatore, Luigi Del Vecchio, Monica Dentice, Giuseppina Mancino, Maria Angela De Stefano, Endocrinology Laboratory, AGEM - Endocrinology, metabolism and nutrition, Miro, C., Di Cicco, E., Ambrosio, R., Mancino, G., Di Girolamo, D., Cicatiello, A. G., Sagliocchi, S., Nappi, A., De Stefano, M. A., Luongo, C., Antonini, D., Visconte, F., Varricchio, S., Ilardi, G., Del Vecchio, L., Staibano, S., Boelen, A., Blanpain, C., Missero, C., Salvatore, D., and Dentice, M.
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0301 basic medicine ,Cell biology ,Molecular biology ,Science ,Cell ,General Physics and Astronomy ,Biology ,Article ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Endocrinology ,0302 clinical medicine ,medicine ,Carcinoma ,Chimie ,Epithelial–mesenchymal transition ,lcsh:Science ,Cancer ,Multidisciplinary ,Physique ,Cadherin ,Thyroid ,Mesenchymal stem cell ,General Chemistry ,Astronomie ,medicine.disease ,3. Good health ,Technologie de l'environnement, contrôle de la pollution ,030104 developmental biology ,medicine.anatomical_structure ,Tumor progression ,030220 oncology & carcinogenesis ,Cancer research ,lcsh:Q ,Hormone - Abstract
Epithelial tumor progression often involves epithelial-mesenchymal transition (EMT). We report that increased intracellular levels of thyroid hormone (TH) promote the EMT and malignant evolution of squamous cell carcinoma (SCC) cells. TH induces the EMT by transcriptionally up-regulating ZEB-1, mesenchymal genes and metalloproteases and suppresses E-cadherin expression. Accordingly, in human SCC, elevated D2 (the T3-producing enzyme) correlates with tumor grade and is associated with an increased risk of postsurgical relapse and shorter disease-free survival. These data provide the first in vivo demonstration that TH and its activating enzyme, D2, play an effective role not only in the EMT but also in the entire neoplastic cascade starting from tumor formation up to metastatic transformation, and supports the concept that TH is an EMT promoter. Our studies indicate that tumor progression relies on precise T3 availability, suggesting that pharmacological inactivation of D2 and TH signaling may suppress the metastatic proclivity of SCC., SCOPUS: ar.j, info:eu-repo/semantics/published
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- 2019
16. The thyroid hormone activating enzyme, type 2 deiodinase, induces myogenic differentiation by regulating mitochondrial metabolism and reducing oxidative stress
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Annunziata Gaetana Cicatiello, Raffaele Ambrosio, Domenico Salvatore, Monica Dentice, Maddalena Raia, Daniela Di Girolamo, Emery Di Cicco, Cristina Luongo, Giuseppina Mancino, Maria Angela De Stefano, Ann Marie Zavacki, Simona Paladino, Annarita Nappi, Caterina Miro, Ashley N. Ogawa-Wong, Serena Sagliocchi, Sagliocchi, Serena, Cicatiello, A. G., Di Cicco, E., Ambrosio, R., Miro, C., Di Girolamo, D., Nappi, Annarita, Mancino, G., De Stefano, M. A., Luongo, C., Raia, M., Ogawa-Wong, A. N., Zavacki, A. M., Paladino, S., Salvatore, Domenico, and Dentice, M.
- Subjects
0301 basic medicine ,Mitochondrial ROS ,Male ,Thyroid Hormones ,Cellular respiration ,Clinical Biochemistry ,Deiodinase ,SOD2 ,Oxidative phosphorylation ,medicine.disease_cause ,Muscle Development ,Biochemistry ,Iodide Peroxidase ,Antioxidants ,Oxidative Phosphorylation ,03 medical and health sciences ,Mice ,0302 clinical medicine ,medicine ,Animals ,lcsh:QH301-705.5 ,chemistry.chemical_classification ,Reactive oxygen species ,lcsh:R5-920 ,biology ,Superoxide Dismutase ,Organic Chemistry ,Cell biology ,Mitochondria ,Oxidative Stress ,030104 developmental biology ,chemistry ,lcsh:Biology (General) ,biology.protein ,Reactive Oxygen Species ,lcsh:Medicine (General) ,Glycolysis ,Oxidation-Reduction ,030217 neurology & neurosurgery ,Oxidative stress ,Intracellular ,Research Paper - Abstract
Thyroid hormone (TH) is a key metabolic regulator that acts by coordinating short- and long-term energy needs. Accordingly, significant metabolic changes are observed depending on thyroid status. Although it is established that hyperthyroidism augments basal energy consumption, thus resulting in an enhanced metabolic state, the net effects on cellular respiration and generation of reactive oxygen species (ROS) remain unclear. To elucidate the effects of augmented TH signal in muscle cells, we generated a doxycycline-inducible cell line in which the expression of the TH-activating enzyme, type 2 deiodinase (D2), is reversibly turned on by the "Tet-ON" system. Interestingly, increased intracellular TH caused a net shift from oxidative phosphorylation to glycolysis and a consequent increase in the extracellular acidification rate. As a result, mitochondrial ROS production, and both the basal and doxorubicin-induced production of cellular ROS were reduced. Importantly, the expression of a set of antioxidant genes was up-regulated, and, among them, the mitochondrial scavenger Sod2 was specifically induced at transcriptional level by D2-mediated TH activation. Finally, we observed that attenuation of oxidative stress and increased levels of SOD2 are key elements of the differentiating cascade triggered by TH and D2, thereby establishing that D2 is essential in coordinating metabolic reprogramming of myocytes during myogenic differentiation. In conclusion, our findings indicate that TH plays a key role in oxidative stress dynamics by regulating ROS generation. Our novel finding that TH and its intracellular metabolism act as mitochondrial detoxifying agents sheds new light on metabolic processes relevant to muscle physiology.
- Published
- 2019
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