PhD Graduate

PhD program:: XXXIII

advisor: Prof. Francesca Cutruzzolà
co-supervisor: Prof. Francesca Cutruzzolà

Thesis title: Role of one-carbon metabolism and cytosolic serine hydroxymethyltransferase in the brain metastatic potential of lung adenocarcinoma.

Metastatic cancer represents the major leading cause responsible for cancer mortality. The tumor microenvironment and the metabolites released by the cells of the target organs play a critical role in metastasis initiation and progression. Lung cancer is a highly aggressive tumor with poor prognosis, which often spreads to the brain. In the present work, we aimed to study the connection between the metabolism of selected amino acids produced and released in the brain and the establishment of metastases from lung cancer. Analysis of the metabolic features of lung metastases reveals that specific amino acids are able to control lung cancer metastatic potential and shed light on the role of serine and glycine. We demonstrate that these non-essential amino acids are required to ensure the motility of lung cancer cells, thus supporting the idea that formation of brain metastasis might depend on serine/glycine one-carbon metabolism (OCM). We show that motility depends on the activity of the cytosolic enzyme serine hydroxymethyltransferase (SHMT1), a key enzyme involved in the OCM, which converts glycine to serine in the cytosol. A specific level of cytosolic serine is required to maintain ATP resources, mainly by acting on glycolysis, and control redox homeostasis. This metabolic status is in turn sensed by AMP kinase (AMPK), which ultimately allows actin filaments polymerization, cytoskeleton remodeling and finally lung cancer cells migration. These results suggest that new therapeutic strategies can be designed using specific inhibitors of serine/glycine import and/or inhibitors of SHMT activity to control metastasis formation.

Research products

11573/1616528 - 2022 - Anticancer activity of (S)-5-Chloro-3-((3,5-dimethylphenyl)sulfonyl)-N-(1-oxo-1-((pyridin-4-ylmethyl)amino)propan-2-yl)-1H-indole-2-carboxamide (RS4690), a new dishevelled 1 inhibitor
Coluccia, Antonio; Bufano, Marianna; La Regina, Giuseppe La; Puxeddu, Michela; Toto, Angelo; Paone, Alessio; Bouzidi, Amani; Musto, Giorgia; Badolati, Nadia; Orlando, Viviana; Biagioni, Stefano; Masci, Domiziana; Cantatore, Chiara; Cirilli, Roberto; Cutruzzolà, Francesca; Gianni, Stefano; Stornaiuolo, Mariano; Silvestri, Romano - 01a Articolo in rivista
paper: CANCERS (Basel: MDPI) pp. - - issn: 2072-6694 - wos: WOS:000773498900001 (4) - scopus: 2-s2.0-85131007159 (4)

11573/1553790 - 2021 - The emerging role of amino acids of the brain microenvironment in the process of metastasis formation
Cutruzzola', Francesca; Bouzidi, Amani; Liberati, Francesca Romana; Spizzichino, Sharon; Boumis, Giovanna; Macone, Alberto; Rinaldo, Serena; Giardina, Giorgio; Paone, Alessio - 01g Articolo di rassegna (Review)
paper: CANCERS (Basel: MDPI) pp. - - issn: 2072-6694 - wos: WOS:000666104500001 (2) - scopus: 2-s2.0-85107408621 (4)

11573/1551305 - 2021 - Importance of amino acids in brain parenchyma invasion by cancer cells
Paone, Alessio; Bouzidi, Amani; Rinaldo, Serena; Giardina, Giorgio; Cutruzzolà, Francesca - 01a Articolo in rivista
paper: ONCOSCIENCE (Impact Journals LLC -) pp. 47-49 - issn: 2331-4737 - wos: (0) - scopus: (0)

11573/1463758 - 2020 - Cytosolic serine hydroxymethyltransferase controls lung adenocarcinoma cells migratory ability by modulating AMP kinase activity
Bouzidi, Amani; Magnifico, Maria Chiara; Paiardini, Alessandro; Macone, Alberto; Boumis, Giovanna; Giardina, Giorgio; Rinaldo, Serena; Liberati, Francesca Romana; Lauro, Clotilde; Limatola, Cristina; Lanzillotta, Chiara; Tramutola, Antonella; Perluigi, Marzia; Sgarbi, Gianluca; Solaini, Giancarlo; Baracca, Alessandra; Paone, Alessio; Cutruzzolà, Francesca - 01a Articolo in rivista
paper: CELL DEATH & DISEASE (Nature Group) pp. - - issn: 2041-4889 - wos: WOS:000595956300001 (9) - scopus: 2-s2.0-85096677891 (10)

11573/1244108 - 2019 - The moonlighting RNA-binding activity of cytosolic serine hydroxymethyltransferase contributes to control compartmentalization of serine metabolism
Guiducci, Giulia; Paone, Alessio; Tramonti, Angela; Giardina, Giorgio; Rinaldo, Serena; Bouzidi, Amani; Magnifico, Maria C; Marani, Marina; Menendez, Javier A; Fatica, Alessandro; Macone, Alberto; Armaos, Alexandros; Tartaglia, Gian G; Contestabile, Roberto; Paiardini, Alessandro; Cutruzzolà, Francesca - 01a Articolo in rivista
paper: NUCLEIC ACIDS RESEARCH (Oxford University Press:Journals Department, Great Clarendon Street, Oxford OX2 6DP United Kingdom:011 44 1865 556767, EMAIL:, INTERNET:, Fax: 011 44 1865 267485 Editore precedente: Information Retrieval ltd., London) pp. 1-16 - issn: 0305-1048 - wos: WOS:000473754300036 (25) - scopus: 2-s2.0-85067847112 (24)

11573/1330042 - 2019 - Linking infection and prostate cancer progression: Toll-like receptor3 stimulation rewires glucose metabolism in prostate cells
Magnifico, M. C.; Macone, A.; Marani, M.; Bouzidi, A.; Giardina, G.; Rinaldo, S.; Cutruzzola, F.; Paone, A. - 01a Articolo in rivista
paper: ANTICANCER RESEARCH (Kapandriti: International Institute of Anticancer Research, 1995 Earliest publisher: Καπανδρίτι: Ιωάννης Γ. Δεληνάσιος, 1981-1995 Kapandriti: Iōannīs G. Delīnasios, 1981-1995) pp. 5541-5549 - issn: 0250-7005 - wos: WOS:000488512600028 (6) - scopus: 2-s2.0-85072761348 (6)

11573/1143149 - 2018 - The catalytic activity of serine hydroxymethyltransferase is essential for de novo nuclear dTMP synthesis in lung cancer cells
Giardina, Giorgio; Paone, Alessio; Tramonti, Angela; Lucchi, Roberta; Marani, Marina; Magnifico, Maria Chiara; Bouzidi, Amani; Pontecorvi, Valentino; Guiducci, Giulia; Zamparelli, Carlotta; Rinaldo, Serena; Paiardini, Alessandro; Contestabile, Roberto; Cutruzzolà, Francesca - 01a Articolo in rivista
paper: THE FEBS JOURNAL (Blackwell Pub., Oxford, UK) pp. 3238-3253 - issn: 1742-464X - wos: WOS:000443814200008 (23) - scopus: 2-s2.0-85052452668 (25)

11573/1131469 - 2018 - Differential inhibitory effect of a pyrazolopyran compound on human serine hydroxymethyltransferase-amino acid complexes
Tramonti, Angela; Paiardini, Alessandro; Paone, Alessio; Bouzidi, Amani; Giardina, Giorgio; Guiducci, Giulia; Magnifico, Maria Chiara; Rinaldo, Serena; Mcdermott, Lee; Menendez, Javier A.; Contestabile, Roberto; Cutruzzolà, Francesca - 01a Articolo in rivista
paper: ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS (Attuale:ELSEVIER SCIENCE INC, 360 PARK AVE SOUTH, NEW YORK, USA, NY, 10010-1710 Academic Press Incorporated:6277 Sea Harbor Drive:Orlando, FL 32887:(800)543-9534, (407)345-4100, EMAIL:, INTERNET:, Fax: (407)352-3445) pp. 71-79 - issn: 0003-9861 - wos: WOS:000442192500007 (13) - scopus: 2-s2.0-85049429016 (13)

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