SIRT7 promotes lung cancer progression by destabilizing the tumor suppressor ARF
Kumari, Poonam (Max-Planck-Institute for Heart and Lung Research. Department of Cardiac Development and Remodeling)
Tarighi, Shahriar (Max-Planck-Institute for Heart and Lung Research. Department of Cardiac Development and Remodeling)
Fuchshuber, Eva (Max-Planck-Institute for Heart and Lung Research. Department of Cardiac Development and Remodeling)
Li, Luhan (Nankai University)
Fernández-Duran, Irene (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Wang, Meilin (Nankai University)
Ayoson, Joshua (Max-Planck-Institute for Heart and Lung Research. Department of Cardiac Development and Remodeling)
Castelló-García, Jose Manuel (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Gámez-García, Andrés (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Espinosa-Alcantud, María Dolores (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Sreenivasan, Krishnamoorthy (Max-Planck-Institute for Heart and Lung Research. Department of Cardiac Development and Remodeling)
Guenther, Stefan (Max-Planck-Institute for Heart and Lung Research. Department of Cardiac Development and Remodeling)
Olivella, Mireia (Institut de Recerca i Innovació en Ciències de la Vida i de la Salut a la Catalunya Central)
Savai, Rajkumar (Justus Liebig University)
Yue, Shijing (Nankai University)
Vaquero, Alejandro (Max-Planck-Institute for Heart and Lung Research. Department of Cardiac Development and Remodeling)
Braun, Thomas (Max-Planck-Institute for Heart and Lung Research. Department of Cardiac Development and Remodeling)
Ianni, Alessandro (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)

Date:	2024
Abstract:	Sirtuin 7 (SIRT7) is a member of the mammalian family of nicotinamide adenine dinucleotide (NAD)-dependent histone/protein deacetylases, known as sirtuins. It acts as a potent oncogene in numerous malignancies, but the molecular mechanisms employed by SIRT7 to sustain lung cancer progression remain largely uncharacterized. We demonstrate that SIRT7 exerts oncogenic functions in lung cancer cells by destabilizing the tumor suppressor alternative reading frame (ARF). SIRT7 directly interacts with ARF and prevents binding of ARF to nucleophosmin, thereby promoting proteasomal-dependent degradation of ARF. We show that SIRT7-mediated degradation of ARF increases expression of protumorigenic genes and stimulates proliferation of non-small-cell lung cancer (NSCLC) cells both in vitro and in vivo in a mouse xenograft model. Bioinformatics analysis of transcriptome data from human lung adenocarcinomas revealed a correlation between SIRT7 expression and increased activity of genes normally repressed by ARF. We propose that disruption of SIRT7-ARF signaling stabilizes ARF and thus attenuates cancer cell proliferation, offering a strategy to mitigate NSCLC progression.
Grants:	European Commission 101065013 Agencia Estatal de Investigación PID2020-117284RB-I00
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	ARF ; SIRT7 ; Sirtuins ; Lung cancer ; Nucleophosmin
Published in:	Proceedings of the National Academy of Sciences of the United States of America, Vol. 121 Núm. 25 (June 2024) , ISSN 1091-6490

DOI: 10.1073/pnas.2409269121
PMID: 38870055

12 p, 9.6 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
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Articles > Published articles