Aboulouard, S.

Bravaccini, S.

Cavallo, V.

Damato, M.

De Summa, S.

Fonzi, E.

Fournier, I.

Gaballo, A.

Giudetti, A.M.

Magnani, L.

Pantalone, L.

Pirini, F.

Puccetti, M.

Salzet, M.

Saponaro, C.

Schirosi, L.

Sergi, D.

Siculella, L.

Stanca, E.

Tacconi, S.

Tebaldi, M.

Tinelli, A.

Trerotola, M.

Vergara, D.

Zito, F.A.

English

Università del Salento: ESE - Salento University Publishing

LEbiotec VI edition – Lecce 27-29 September 2023 – Abstract Book  38  Protein Kinase C activation regulates NDRG1 expression  Saponaro C1, Damato M2, Stanca E2, Cavallo V2, Aboulouard S3, Zito FA1, De Summa S4, Schirosi L1, Bravaccini S5, Pirini F5, Fonzi E, Tebaldi M, Puccetti M6, Gaballo A7, Pantalone L8,9, Magnani L10, Sergi D11, Tinelli A12, Tacconi S13, Giudetti AM2, Siculella L2, Fournier I3, Salzet M3, Trerotola M8,9#, Vergara D2#*  1 Pathology Department, IRCCS Istituto Tumori "Giovanni Paolo II", 70124 Bari, Italy 2 Department of Biological and Environmental Sciences and Technologies (DiSTeBA), University of Salento, Lecce, Italy 3 Univ. Lille, Inserm, CHU Lille, U1192, Laboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse (PRISM), Lille, France 4 Molecular Diagnostics and Pharmacogenetics Unit, IRCCS Istituto Tumori "Giovanni Paolo II", 70124 Bari, Italy 5 Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy 6 Azienda Unità Sanitaria Locale di Imola, Imola, Italy 7 CNR Nanotec, Institute of Nanotechnology, Via Monteroni, 73100 Lecce, Italy 8 Laboratory of Cancer Pathology, Center for Advanced Studies and Technology (CAST), "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy 9 Department of Medical, Oral and Biotechnological Sciences, "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy 10 Department of Surgery and Cancer, Imperial College London, London, UK 11 Department of Radiology - V. Fazzi Hospital, 73100 Lecce, Italy 12 Department of Obstetrics and Gynecology and CERICSAL (CEntro di RIcerca Clinico SALentino), “Veris delli Ponti Hospital”, Scorrano, 73020, Scorrano (Lecce), Italy 13 CarMeN Laboratory (UMR INSERM 1060/INRA 1397), Lyon-Sud Faculty of Medicine, University of Lyon, Pierre-Bénite, France # co-last authors    N-myc downstream regulated gene 1 (NDRG1) is a member of the NDRG family of intracellular proteins, and plays a central role in a wide range of biological processes including stress response, differentiation, and maintenance of the myelin sheath. The overexpression of NDRG1 is an indicator of poor prognosis in various pathological conditions. Here, we found that NDRG1 is an independent prognostic marker of poor outcome in breast cancer (BC). The relationship with an aggressive phenotype was underlined by the survival analysis, where Kaplan-Meier curves showed a worse clinical outcome in the subgroup of Triple Negative BC (TNBC) with high NDRG1 expression. In vitro, CRISPR-based inactivation of NDRG1 allowed us to demonstrate that this protein is required for breast cancer cell invasion, without affecting viability. NDRG1 expression is regulated by a variety of molecular mechanisms, including transcriptional and post-translational control. We observed that different acute stress conditions converge on protein kinase C (PKC) activation driving enhanced NDRG1 expression through a signaling pathway that involves ROCK/AMPK/Akt kinases. This newly discovered mechanism was specific for LEbiotec VI edition – Lecce 27-29 September 2023 – Abstract Book  39  NDRG1 as the expression of other NDRG members was not affected. Together, our results suggest that pathophysiological PKC-mediated activation of NDRG1 may be a response mechanism to metabolic stress and anticancer agents.   

Protein Kinase C activation regulates NDRG1 expression

ESE - Salento University Publishing

http://siba-ese.unile.it/index.php/lebiotec/article/download/28183/23102

Protein Kinase C activation regulates NDRG1 expression

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Università del Salento: ESE - Salento University Publishing

ESE - Salento University Publishing