NOEMI MONTI

Dottoressa di ricerca

ciclo: XXXV


supervisore: Prof. Mariano Bizzarri

Titolo della tesi: Myo-inositol affects the cell-commitment induced by TGF-β in MCF-10A cells and primary mammary fibroblasts

Cells are characterized by intrinsic phenotypic plasticity. Waddington was the first to introduce the concept of “epigenetic landscape” to indicate the ability of a cell to progress from one differentiated state to another. The underlying cellular commitment is due to a wide range of factors, including molecular and microenvironmental constraints. Indeed, under specific conditions, cells can undergo trans-differentiation processes, losing their typical molecular and morphological characteristics to acquire others in response to stimuli of different natures. One of these possible stimuli is TGF-β, a pleiotropic cytokine able to regulate several biological processes. In particular, TGF-β is the main inducer of two trans-differentiation phenomena: the epithelial-mesenchymal transition (EMT) and the activation of fibroblasts into myo-fibroblasts. EMT is a trans-differentiation program by which epithelial cells lose cell-cell adhesion and acquire migratory and invasive properties, specific features of mesenchymal cells. The trans-differentiation of fibroblasts into myo-fibroblasts occurs under physiological conditions, such as during tissue repair, but also under pathological conditions, and it can lead to organ fibrosis and eventually to organ failure. Both of these trans-differentiation phenomena are closely linked to tumor development and progression. In previous works, we demonstrated that myo-inositol is able to affect cell morphology by remodeling the cytoskeleton in a highly metastatic and invasive cell line. The principal aim of this work is to highlight the cell fate of MCF-10A epithelial breast cells and of primary mammary fibroblasts upon treatment with TGF-β for several days. The second objective is to evaluate whether myo-inositol, a polyol, is able to regulate the cell commitment induced by TGF-β. To achieve these purposes, we treated MCF-10A with TGF-β for up to five days. Treatment with TGF-β triggers EMT, as demonstrated by changes in functional (increased motility and invasiveness) and morphological (transition from a cuboidal to an elongated shape) parameters. These modifications corresponded to concomitant changes in the main molecular pathways responsible for the regulation of EMT, including reduction of the expression of epithelial markers, such as E-cadherin, and keratin 18, and the increase of mesenchymal ones such as Snai1, N-cadherin and vimentin. In the meanwhile, we treated the primary fibroblasts with TGF-β for 72 hours, and we highlighted the trans-differentiation into myo-fibroblasts (the cells are more flattened and scattered), remodeling of the cytoskeleton, and increase of molecular parameters, such as the synthesis and production of the extracellular matrix components. However, the trans-differentiation induced by TGF-β in MCF-10A and primary fibroblasts can be blocked and induced towards an almost complete reversion by the addition of myo-inositol. Following treatment with myo-inositol, EMT-induced MCF-10A lose most of their mesenchymal characteristics and recover a normal epithelial phenotype, both from a morphological and functional point of view. In particular, the reversion induced by inositol dramatically affects both the motility and invasiveness of the cells and almost normalizes the molecular parameters. On the other hand, myo-fibroblasts treated with myo-inositol decrease the synthesis and the production of matrix components, and recover a less invasive and migratory phenotype. Therefore, the results obtained demonstrate that: 1) treatment with TGF-β triggers a trans-differentiation program that leads the cells to assume an unstable phenotype with different morphological and functional characteristics; 2) this phenotype can be almost completely abolished by treatment with myo-inositol with the recovery of normal morphological and functional features.

Produzione scientifica

11573/1718186 - 2024 - Inositol Restores Appropriate Steroidogenesis in PCOS Ovaries Both In Vitro and In Vivo Experimental Mouse Models
Fedeli, Valeria; Unfer, Vittorio; Dinicola, Simona; Simone Laganà, Antonio; Canipari, Rita; Monti, Noemi; Querqui, Alessandro; Galante, Emanuele; Laurenzi, Gaia; Bizzarri, Mariano - 01a Articolo in rivista
rivista: CELLS (Basel: mdpi-Molecular Diversity Preservation International) pp. 1-19 - issn: 2073-4409 - wos: WOS:001276627200001 (0) - scopus: 2-s2.0-85199583541 (0)

11573/1700319 - 2024 - System biology approach in investigating epithelial-mesenchymal transition (EMT)
Monti, Noemi; Querqui, Alessandro; Lentini, Guglielmo; Tafani, Marco; Bizzarri, Mariano - 02a Capitolo o Articolo
libro: Systems Biology - (978-1-0716-3576-6; 978-1-0716-3577-3)

11573/1682463 - 2023 - Myo-inositol and D-chiro-inositol as modulators of ovary steroidogenesis: a narrative review
Bizzarri, Mariano; Monti, Noemi; Piombarolo, Aurora; Angeloni, Antonio; Verna, Roberto - 01g Articolo di rassegna (Review)
rivista: NUTRIENTS (Basel, Switzerland: Molecular Diversity Preservation International (MDPI)) pp. 1-14 - issn: 2072-6643 - wos: WOS:000977260800001 (13) - scopus: 2-s2.0-85156180318 (11)

11573/1678015 - 2023 - Myo-inositol reverses TGF-β1-induced EMT in MCF-10A non-tumorigenic breast cells
Monti, Noemi; Dinicola, Simona; Querqui, Alessandro; Fabrizi, Gianmarco; Fedeli, Valeria; Gesualdi, Luisa; Catizone, Angiolina; Unfer, Vittorio; Bizzarri, Mariano - 01a Articolo in rivista
rivista: CANCERS (Basel: MDPI) pp. 1-19 - issn: 2072-6694 - wos: WOS:000980913000001 (2) - scopus: 2-s2.0-85153876283 (3)

11573/1617836 - 2022 - Microgravity modifies the phenotype of fibroblast and promotes remodeling of the fibroblast–keratinocyte interaction in a 3D co-culture model
Fedeli, Valeria; Cucina, Alessandra; Dinicola, Simona; Fabrizi, Gianmarco; Catizone, Angiolina; Gesualdi, Luisa; Ceccarelli, Simona; Halim Harrath, Abdel; Alwasel, Saleh H.; Ricci, Giulia; Pedata, Paola; Bizzarri, Mariano; Monti, Noemi - 01a Articolo in rivista
rivista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (Basel: MDPI Center) pp. 1-22 - issn: 1422-0067 - wos: WOS:000762469000001 (10) - scopus: 2-s2.0-85124612813 (12)

11573/1682286 - 2022 - Paradoxical behavior of oncogenes undermines the somatic mutation theory
Monti, Noemi; Verna, Roberto; Piombarolo, Aurora; Querqui, Alessandro; Bizzarri, Mariano; Fedeli, Valeria - 01a Articolo in rivista
rivista: BIOMOLECULES (Basel: MDPI) pp. 1-15 - issn: 2218-273X - wos: WOS:000804903700001 (9) - scopus: 2-s2.0-85129196427 (10)

11573/1617951 - 2022 - Does Alpha-lipoic acid improve effects on polycystic ovary syndrome?
Simone Laganà, Antonio; Monti, Noemi; Fedeli, Valeria; Gullo, Giuseppe; Bizzarri, Mariano - 01a Articolo in rivista
rivista: EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES (Roma: Verduci publisher) pp. 1241-1247 - issn: 2284-0729 - wos: WOS:000763332500024 (20) - scopus: 2-s2.0-85125795949 (23)

11573/1590058 - 2021 - Personalization of medical treatments in oncology: time for rethinking the disease concept to improve individual outcomes
Bizzarri, M.; Fedeli, V.; Monti, N.; Cucina, A.; Jalouli, M.; Alwasel, S. H.; Harrath, A. H. - 01g Articolo di rassegna (Review)
rivista: THE EPMA JOURNAL (Dordrecht : Springer Netherlands) pp. 1-14- - issn: 1878-5085 - wos: WOS:000705790900001 (8) - scopus: 2-s2.0-85116777794 (8)

11573/1545100 - 2021 - PCOS and inositols: controversial results and necessary clarifications. Basic differences between D-chiro and myo-inositol
Monastra, Giovanni; Vucenik, Ivana; Halim Harrath, Abdel; Alwasel, Saleh H.; Kamenov, Zdravko A.; Simone Laganà, Antonio; Monti, Noemi; Fedeli, Valeria; Bizzarri, Mariano - 01a Articolo in rivista
rivista: FRONTIERS IN ENDOCRINOLOGY (Lausanne : Frontiers Research Foundation, 2010-) pp. - - issn: 1664-2392 - wos: WOS:000641265200001 (15) - scopus: 2-s2.0-85104685129 (22)

11573/1487101 - 2021 - Survival pathways are differently affected by microgravity in normal and cancerous breast cells
Monti, N.; Masiello, M. G.; Proietti, S.; Catizone, A.; Ricci, G.; Harrath, A. H.; Alwasel, S. H.; Cucina, A.; Bizzarri, M. - 01a Articolo in rivista
rivista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (Basel (Matthaeustrasse 11) : Molecular Diversity Preservation International MDPI) pp. 1-26 - issn: 1661-6596 - wos: WOS:000611351500001 (19) - scopus: 2-s2.0-85099542244 (20)

11573/1442522 - 2020 - Constraints Shape Cell Function and Morphology by Canalizing the Developmental Path along the Waddington's Landscape
Bizzarri, Mariano; Giuliani, Alessandro; Minini, Mirko; Monti, Noemi; Cucina, Alessandra - 01a Articolo in rivista
rivista: BIOESSAYS (-HOBOKEN, USA, NJ: JOHN WILEY & SONS INC -Cambridge : Cambridge University Press, 1984-) pp. 1900108- - issn: 0265-9247 - wos: WOS:000516656800001 (8) - scopus: 2-s2.0-85081231084 (9)

11573/1682459 - 2020 - Rediscovery of natural compounds acting via multitarget recognition and noncanonical pharmacodynamical actions
Bizzarri, Mariano; Giuliani, Alessandro; Monti, Noemi; Verna, Roberto; Pensotti, Andrea; Cucina, Alessandra - 01g Articolo di rassegna (Review)
rivista: DRUG DISCOVERY TODAY (Amsterdam: Elsevier) pp. 920-927 - issn: 1878-5832 - wos: WOS:000541749200013 (9) - scopus: 2-s2.0-85081693660 (10)

11573/1499669 - 2020 - A challenging task—how to successfully separate theca and granulosa cells: a mandatory step for investigating ovary steroidogenesis
Fedeli, Valeria; Monti, Noemi; Canipari, Rita - 01a Articolo in rivista
rivista: ORGANISMS (Roma: Sapienza Università di Roma) pp. 86-89 - issn: 2532-5876 - wos: (0) - scopus: (0)

11573/1401433 - 2020 - Cpg and non-Cpg presenilin1 methylation pattern in course of neurodevelopment and neurodegeneration is associated with gene expression in human and murine brain
Monti, N.; Cavallaro, R. A.; Stoccoro, A.; Nicolia, V.; Scarpa, S.; Kovacs, G. G.; Fiorenza, M. T.; Lucarelli, M.; Aronica, E.; Ferrer, I.; Coppede, F.; Troen, A. M.; Fuso, A. - 01a Articolo in rivista
rivista: EPIGENETICS (Georgetown, TX : Landes Bioscience,) pp. 781-799 - issn: 1559-2294 - wos: WOS:000512864300001 (40) - scopus: 2-s2.0-85079070945 (48)

11573/1500633 - 2020 - Fibrosis: a role for vitamin D
Monti, Noemi; Cucina, Alessandra - 01a Articolo in rivista
rivista: ORGANISMS (Roma: Sapienza Università di Roma) pp. 26-41 - issn: 2532-5876 - wos: (0) - scopus: (0)

11573/1340607 - 2019 - Reproducibility crisis. Impact on uncontrolled release of nutraceutical preparations
Bizzarri, Mariano; Monti, Noemi - 01a Articolo in rivista
rivista: ORGANISMS (Roma: Sapienza Università di Roma) pp. - - issn: 2532-5876 - wos: (0) - scopus: (0)

11573/1340363 - 2019 - Myo-Inositol treatment inhibits motility in triple negative breast cancer via miR-125a-5p/IP6K1 axis
Minini, Mirko; Proietti, Sara; He, Xingkang; Senni, Alice; Monti, Noemi; Fuso, Andrea; Cucina, Alessandra; Cao, Yihai; Bizzarri, Mariano - 04b Atto di convegno in volume
congresso: EMBL CONFERENCE: Cancer Genomics (EMBL Heidelberg, Germany)
libro: EMBL CONFERENCE: Cancer Genomics - ()

11573/1340369 - 2019 - The activation of miR-125a-5p/IP6K1 axis in breast cancer cells upon treatment with myo-Inositol.
Minini, Mirko; Proietti, Sara; Monti, Noemi; Senni, Alice; Fuso, Andrea; Cucina, Alessandra; Bizzarri, Mariano - 04b Atto di convegno in volume
congresso: 16th Horizons in Molecular Biology, International PhD Student Symposium and Career Fair for Life Sciences (MPI, Göttingen, Germany)
libro: 16th Horizons in Molecular Biology, International PhD Student Symposium and Career Fair for Life Sciences - ()

11573/1276721 - 2019 - Active fraction from embryo fish extracts induces reversion of the malignant invasive phenotype in breast cancer through down-regulation of TCTP and modulation of E-cadherin/β-catenin pathway
Proietti, Sara; Cucina, Alessandra; Pensotti, Andrea; Biava, Pier Mario; Minini, Mirko; Monti, Noemi; Catizone, Angela; Ricci, Giulia; Leonetti, Erica; Harrath, Abdel Halim; Alwasel, Saleh H; Bizzarri, Mariano - 01a Articolo in rivista
rivista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (Basel: MDPI Center) pp. 1-18 - issn: 1422-0067 - wos: WOS:000469753500098 (19) - scopus: 2-s2.0-85065656863 (20)

11573/692461 - 2013 - Complex expression of BDNF and reelin in the developing and adult brain of TgCRND8 mice
Fuso, Andrea; Nicolia, Vincenzina; Canterini, Sonia; Monti, Noemi; Ciraci, Viviana; Palladino, Giampiero; Cavallaro, Rosaria Adele; Fiorenza, Maria Teresa; Scarpa, Sigfrido - 04b Atto di convegno in volume
congresso: AAIC (Boston, United States)

11573/1340352 - 2013 - Genotype, age and gender interaction in regulating BDNF expression in TgCRND8 Alzheimer's disease mice
Monti, Noemi; Ciraci, V; Fuso, A; Canterini, S; Nicolia, V; Palladino, G; Cavallaro, Ra; Mangia, F; Fiorenza, Mt; Scarpa, S. - 04b Atto di convegno in volume
congresso: National congress of the italian society of neuroscience. (Rome, Italy)
libro: National congress of the italian society of neuroscience. - ()

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