Unraveling the protein kinase C/NDRG1 signaling network in breast cancer
Abstract 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 metabolism. The overexpression of NDRG1 is an indicator of poor prognosis in va...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-12-01
|
| Series: | Cell & Bioscience |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13578-024-01336-z |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841559104798064640 |
|---|---|
| author | C. Saponaro M. Damato E. Stanca S. Aboulouard F. A. Zito S. De Summa D. Traversa L. Schirosi S. Bravaccini F. Pirini E. Fonzi M. Tebaldi M. Puccetti A. Gaballo L. Pantalone M. Ronci L. Magnani D. Sergi A. Tinelli S. Tacconi L. Siculella A. M. Giudetti I. Fournier M. Salzet M. Trerotola D. Vergara |
| author_facet | C. Saponaro M. Damato E. Stanca S. Aboulouard F. A. Zito S. De Summa D. Traversa L. Schirosi S. Bravaccini F. Pirini E. Fonzi M. Tebaldi M. Puccetti A. Gaballo L. Pantalone M. Ronci L. Magnani D. Sergi A. Tinelli S. Tacconi L. Siculella A. M. Giudetti I. Fournier M. Salzet M. Trerotola D. Vergara |
| author_sort | C. Saponaro |
| collection | DOAJ |
| description | Abstract 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 metabolism. The overexpression of NDRG1 is an indicator of poor prognosis in various types of cancer. Here, we found that NDRG1 is an independent prognostic marker of poor outcome in breast cancer (BC). Analysis of the TCGA dataset showed a significant positive correlation between NDRG1 and PRKCA expression, suggesting a mechanistic role of protein kinase C (PKC) in the regulation of NDRG1. We then assessed the hypothesis that PKC might modulate the activity of NDRG1, and observed that different acute stress conditions converging on PKC activation lead to enhanced NDRG1 expression. This mechanism was found to be specific for NDRG1 as the expression of other NDRG members was not affected. Moreover, CRISPR-based inhibition of NDRG1 expression was obtained in a BC cell line, and showed that this protein is a key driver of BC cell invasion through the Rho-associated coiled-coil containing protein kinase 1 (ROCK1)/phosphorylated cofilin pathway that regulates stress fiber assembly, and the modulation of extracellular matrix reorganization related genes. Together, our findings highlight the potential of NDRG1 as a new BC biomarker and uncover a novel mechanism of regulation of NDRG1 expression that might lead to innovative therapeutic strategies. |
| format | Article |
| id | doaj-art-e82a2bebc54945e184e0f0f1e98b23d2 |
| institution | Kabale University |
| issn | 2045-3701 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell & Bioscience |
| spelling | doaj-art-e82a2bebc54945e184e0f0f1e98b23d22025-01-05T12:47:53ZengBMCCell & Bioscience2045-37012024-12-0114112210.1186/s13578-024-01336-zUnraveling the protein kinase C/NDRG1 signaling network in breast cancerC. Saponaro0M. Damato1E. Stanca2S. Aboulouard3F. A. Zito4S. De Summa5D. Traversa6L. Schirosi7S. Bravaccini8F. Pirini9E. Fonzi10M. Tebaldi11M. Puccetti12A. Gaballo13L. Pantalone14M. Ronci15L. Magnani16D. Sergi17A. Tinelli18S. Tacconi19L. Siculella20A. M. Giudetti21I. Fournier22M. Salzet23M. Trerotola24D. Vergara25Pathology Department, IRCCS Istituto Tumori “Giovanni Paolo II”Department of Experimental Medicine, University of SalentoDepartment of Experimental Medicine, University of SalentoLaboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse (PRISM), Lille University, Inserm, CHU LillePathology Department, IRCCS Istituto Tumori “Giovanni Paolo II”Molecular Diagnostics and Pharmacogenetics Unit, IRCCS Istituto Tumori “Giovanni Paolo II”Molecular Diagnostics and Pharmacogenetics Unit, IRCCS Istituto Tumori “Giovanni Paolo II”Pathology Department, IRCCS Istituto Tumori “Giovanni Paolo II”Department of Medicine and Surgery, University of Enna “Kore”Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”Unit of Biostatistics and Clinical Trials, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”Unit of Biostatistics and Clinical Trials, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”Azienda Unità Sanitaria Locale di ImolaCNR Nanotec, Institute of NanotechnologyLaboratory of Cancer Pathology, Center for Advanced Studies and Technology (CAST), “G. d’Annunzio” University of Chieti-PescaraLaboratory of Cancer Pathology, Center for Advanced Studies and Technology (CAST), “G. d’Annunzio” University of Chieti-PescaraThe Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer ResearchDepartment of Radiology, V. Fazzi HospitalDepartment of Obstetrics and Gynecology and CERICSAL, (CEntro di RIcerca Clinico SALentino), “Veris Delli Ponti Hospital”Department of Biology and Biotechnology “Charles Darwin”, Sapienza University of RomeDepartment of Experimental Medicine, University of SalentoDepartment of Biological and Environmental Sciences and Technologies (DiSTeBA), University of SalentoLaboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse (PRISM), Lille University, Inserm, CHU LilleLaboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse (PRISM), Lille University, Inserm, CHU LilleLaboratory of Cancer Pathology, Center for Advanced Studies and Technology (CAST), “G. d’Annunzio” University of Chieti-PescaraDepartment of Biological and Environmental Sciences and Technologies (DiSTeBA), University of SalentoAbstract 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 metabolism. The overexpression of NDRG1 is an indicator of poor prognosis in various types of cancer. Here, we found that NDRG1 is an independent prognostic marker of poor outcome in breast cancer (BC). Analysis of the TCGA dataset showed a significant positive correlation between NDRG1 and PRKCA expression, suggesting a mechanistic role of protein kinase C (PKC) in the regulation of NDRG1. We then assessed the hypothesis that PKC might modulate the activity of NDRG1, and observed that different acute stress conditions converging on PKC activation lead to enhanced NDRG1 expression. This mechanism was found to be specific for NDRG1 as the expression of other NDRG members was not affected. Moreover, CRISPR-based inhibition of NDRG1 expression was obtained in a BC cell line, and showed that this protein is a key driver of BC cell invasion through the Rho-associated coiled-coil containing protein kinase 1 (ROCK1)/phosphorylated cofilin pathway that regulates stress fiber assembly, and the modulation of extracellular matrix reorganization related genes. Together, our findings highlight the potential of NDRG1 as a new BC biomarker and uncover a novel mechanism of regulation of NDRG1 expression that might lead to innovative therapeutic strategies.https://doi.org/10.1186/s13578-024-01336-zNDRG1Breast cancerTNBCPKC |
| spellingShingle | C. Saponaro M. Damato E. Stanca S. Aboulouard F. A. Zito S. De Summa D. Traversa L. Schirosi S. Bravaccini F. Pirini E. Fonzi M. Tebaldi M. Puccetti A. Gaballo L. Pantalone M. Ronci L. Magnani D. Sergi A. Tinelli S. Tacconi L. Siculella A. M. Giudetti I. Fournier M. Salzet M. Trerotola D. Vergara Unraveling the protein kinase C/NDRG1 signaling network in breast cancer Cell & Bioscience NDRG1 Breast cancer TNBC PKC |
| title | Unraveling the protein kinase C/NDRG1 signaling network in breast cancer |
| title_full | Unraveling the protein kinase C/NDRG1 signaling network in breast cancer |
| title_fullStr | Unraveling the protein kinase C/NDRG1 signaling network in breast cancer |
| title_full_unstemmed | Unraveling the protein kinase C/NDRG1 signaling network in breast cancer |
| title_short | Unraveling the protein kinase C/NDRG1 signaling network in breast cancer |
| title_sort | unraveling the protein kinase c ndrg1 signaling network in breast cancer |
| topic | NDRG1 Breast cancer TNBC PKC |
| url | https://doi.org/10.1186/s13578-024-01336-z |
| work_keys_str_mv | AT csaponaro unravelingtheproteinkinasecndrg1signalingnetworkinbreastcancer AT mdamato unravelingtheproteinkinasecndrg1signalingnetworkinbreastcancer AT estanca unravelingtheproteinkinasecndrg1signalingnetworkinbreastcancer AT saboulouard unravelingtheproteinkinasecndrg1signalingnetworkinbreastcancer AT fazito unravelingtheproteinkinasecndrg1signalingnetworkinbreastcancer AT sdesumma unravelingtheproteinkinasecndrg1signalingnetworkinbreastcancer AT dtraversa unravelingtheproteinkinasecndrg1signalingnetworkinbreastcancer AT lschirosi unravelingtheproteinkinasecndrg1signalingnetworkinbreastcancer AT sbravaccini unravelingtheproteinkinasecndrg1signalingnetworkinbreastcancer AT fpirini unravelingtheproteinkinasecndrg1signalingnetworkinbreastcancer AT efonzi unravelingtheproteinkinasecndrg1signalingnetworkinbreastcancer AT mtebaldi unravelingtheproteinkinasecndrg1signalingnetworkinbreastcancer AT mpuccetti unravelingtheproteinkinasecndrg1signalingnetworkinbreastcancer AT agaballo unravelingtheproteinkinasecndrg1signalingnetworkinbreastcancer AT lpantalone unravelingtheproteinkinasecndrg1signalingnetworkinbreastcancer AT mronci unravelingtheproteinkinasecndrg1signalingnetworkinbreastcancer AT lmagnani unravelingtheproteinkinasecndrg1signalingnetworkinbreastcancer AT dsergi unravelingtheproteinkinasecndrg1signalingnetworkinbreastcancer AT atinelli unravelingtheproteinkinasecndrg1signalingnetworkinbreastcancer AT stacconi unravelingtheproteinkinasecndrg1signalingnetworkinbreastcancer AT lsiculella unravelingtheproteinkinasecndrg1signalingnetworkinbreastcancer AT amgiudetti unravelingtheproteinkinasecndrg1signalingnetworkinbreastcancer AT ifournier unravelingtheproteinkinasecndrg1signalingnetworkinbreastcancer AT msalzet unravelingtheproteinkinasecndrg1signalingnetworkinbreastcancer AT mtrerotola unravelingtheproteinkinasecndrg1signalingnetworkinbreastcancer AT dvergara unravelingtheproteinkinasecndrg1signalingnetworkinbreastcancer |