ROSA BORDONE

Dottoressa di ricerca

ciclo: XXXIV



Titolo della tesi: A CNBP-PRDM1 axis links intestinal microbiota to MYC-driven Colorectal Tumorigenesis

Colorectal cancer (CRC) is one of the most common neoplasia worldwide and causes more than 900000 deaths every year. CRC etiology is complex and include both genetic and environmental factors such as positive family history, high fat diet, alcohol intake and lack of physical activity. Recent observations have highlighted the potential role of gut microbiota dysbiosis in CRC onset, progression, and metastasis. Changes in the intestinal microbiome composition have been found in patients with colon cancer compared to healthy controls and specific bacterial species correlated to increased risk have been identified. Despite these observations, the mechanism of action underlying the pro-tumorigenicity of these species is still elusive. Recent works revealed that the immune response triggered by microbe-associated molecular patterns (MAMPs) through the Toll Like Receptors (TLRs) pathway could represent a link between microbiome and colon cancer onset. We show that microbiota-derived lipopolysaccharide (LPS) can activate the Cellular Nucleic Binding Protein, CNBP in a Calcineurin dependent manner. LPS stimulation induces the TLR4 signaling cascade resulting in increased intracellular concentration of Ca2+ with consequent activation of the phosphatase Calcineurin (CN). We discovered that CNBP is dephosphorylated by CN in correspondence of a 14-3-3 binding site thus leading to its disassociation from the 14-3-3 proteins and translocation in the nucleus where it can suppress PRDM1 transcription through the unfolding of its G-quadruplexes inducing overexpression of MYC, one of the main drivers in colorectal tumorigenesis. Intestinal dysbiosis, as well as overexpression of the toll like receptor in the intestinal mucosa as a consequence of chronic inflammation, trigger CNBP-mediated suppression of PRDM1 and culminates in the promotion of MYC-driven colon cancer growth.

Produzione scientifica

  • 11573/1674490 - 2023 - Combined inhibition of polyamine metabolism and eIF5A hypusination suppresses colorectal cancer growth through a converging effect on MYC translation (01a Articolo in rivista)
    CONI, SONIA; BORDONE, ROSA; IVY, DEVON MICHAEL; YURTSEVER, ZULEYHA NIHAN; DI MAGNO, LAURA; D'AMICO, RODRIGO; CESARO, BIANCA; FATICA, ALESSANDRO; BELARDINILLI, FRANCESCA; BUFALIERI, FRANCESCA; MARODER, MARELLA; DE SMAELE, ENRICO; DI MARCOTULLIO, LUCIA; GIANNINI, GIUSEPPE; AGOSTINELLI, ENZO; CANETTIERI, GIANLUCA
  • 11573/1210601 - 2019 - Mitogen-activated kinase kinase kinase 1 inhibits hedgehog signaling and medulloblastoma growth through GLI1 phosphorylation (01a Articolo in rivista)
    ANTONUCCI, LAURA; DI MAGNO, LAURA; D'AMICO, DAVIDE; MANNI, SIMONA; SERRAO, SILVIA MARIA; DI PASTENA, FIORELLA; BORDONE, ROSA; YURTSEVER, ZULEYHA NIHAN; CAIMANO, MIRIAM; PETRONI, MARIALAURA; GIORGI, ALESSANDRA; SCHININA', MARIA EUGENIA; DI MARCOTULLIO, LUCIA; DE SMAELE, ENRICO; CHECQUOLO, SAULA; CAPALBO, CARLO; AGOSTINELLI, ENZO; MARODER, MARELLA; CONI, SONIA; CANETTIERI, GIANLUCA
  • 11573/1664745 - 2022 - Induction of Ferroptosis in Glioblastoma and Ovarian Cancers by a New Pyrrole Tubulin Assembly Inhibitor (01a Articolo in rivista)
    PUXEDDU, MICHELA; D'AMBROSIO, MICHELE; NALLI, MARIANNA; COLUCCIA, ANTONIO; MANETTO, SIMONE; CIOGLI, ALESSIA; MASCI, DOMIZIANA; FIONDA, CINZIA; CONI, SONIA; BORDONE, ROSA; CANETTIERI, GIANLUCA; SILVESTRI, ROMANO; LA REGINA, GIUSEPPE
  • 11573/1471575 - 2020 - Blockade of EIF5A hypusination limits colorectal cancer growth by inhibiting MYC elongation (01a Articolo in rivista)
    CONI, SONIA; SERRAO, SILVIA MARIA; YURTSEVER, ZULEYHA NIHAN; DI MAGNO, LAURA; BORDONE, ROSA; BERTANI, CAMILLA; LICURSI, VALERIO; IANNIELLO, ZAIRA; INFANTE, PAOLA; MORETTI, MARTA; PETRONI, MARIALAURA; FATICA, ALESSANDRO; MACONE, ALBERTO; DE SMAELE, ENRICO; DI MARCOTULLIO, LUCIA; GIANNINI, GIUSEPPE; MARODER, MARELLA; AGOSTINELLI, ENZO; CANETTIERI, GIANLUCA
  • 11573/1571355 - 2021 - Translational control of polyamine metabolism by CNBP is required for Drosophila locomotor function (01a Articolo in rivista)
    CONI, SONIA; FALCONIO, FEDERICA ALICE; MARZULLO, MARTA; ZULIANI, BENEDETTA; MOSTI, FEDERICA; FATICA, ALESSANDRO; IANNIELLO, ZAIRA; BORDONE, ROSA; MACONE, ALBERTO; AGOSTINELLI, ENZO; CANETTIERI, GIANLUCA; CIAPPONI, LAURA
  • 11573/1666339 - 2023 - Partial Truncation of the C-Terminal Domain of PTCH1 in Cancer Enhances Autophagy and Metabolic Adaptability (01a Articolo in rivista)
    BORDONE, ROSA; DI MAGNO, LAURA; CANETTIERI, GIANLUCA
  • 11573/1660745 - 2022 - The Mechanism of Action of Biguanides: New Answers to a Complex Question (01g Articolo di rassegna (Review))
    DI MAGNO, LAURA; DI PASTENA, FIORELLA; BORDONE, ROSA; CONI, SONIA; CANETTIERI, GIANLUCA

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