dc.contributor | Vall d'Hebron Barcelona Hospital Campus |
dc.contributor.author | Granado Martinez, Paula |
dc.contributor.author | García Ortega, Sara |
dc.contributor.author | González Sánchez, Elena |
dc.contributor.author | McGrail Fernández, Kimberley Anne |
dc.contributor.author | Selgas Sanchis, Rafael |
dc.contributor.author | Grueso Gragera, Judit |
dc.contributor.author | Gil Villaverde, Rosa |
dc.contributor.author | Naldaiz-Gastesi, Neia |
dc.contributor.author | Rhodes, Ana C |
dc.contributor.author | Hernandez Losa, Javier |
dc.contributor.author | Ferrer Fábrega, Berta |
dc.contributor.author | Canals Suris, Francesc |
dc.contributor.author | Villanueva Cardús, Josep |
dc.contributor.author | Mendez Fernández, Olga |
dc.contributor.author | García-Patos Briones, Vicente |
dc.contributor.author | Recio Conde, Juan Angel |
dc.contributor.author | Muñoz Couselo, Eva |
dc.date.accessioned | 2021-09-03T10:12:27Z |
dc.date.available | 2021-09-03T10:12:27Z |
dc.date.issued | 2020-07-09 |
dc.identifier.citation | Granado-Martínez P, Garcia-Ortega S, González-Sánchez E, McGrail K, Selgas R, Grueso J, et al. STK11 (LKB1) missense somatic mutant isoforms promote tumor growth, motility and inflammation. Commun Biol. 2020 Jul 9;3:366. |
dc.identifier.issn | 2399-3642 |
dc.identifier.uri | https://hdl.handle.net/11351/6261 |
dc.description | Cancer genetics; Lung cancer; Oncogenes |
dc.description.abstract | Elucidating the contribution of somatic mutations to cancer is essential for personalized medicine. STK11 (LKB1) appears to be inactivated in human cancer. However, somatic missense mutations also occur, and the role/s of these alterations to this disease remain unknown. Here, we investigated the contribution of four missense LKB1 somatic mutations in tumor biology. Three out of the four mutants lost their tumor suppressor capabilities and showed deficient kinase activity. The remaining mutant retained the enzymatic activity of wild type LKB1, but induced increased cell motility. Mechanistically, LKB1 mutants resulted in differential gene expression of genes encoding vesicle trafficking regulating molecules, adhesion molecules and cytokines. The differentially regulated genes correlated with protein networks identified through comparative secretome analysis. Notably, three mutant isoforms promoted tumor growth, and one induced inflammation-like features together with dysregulated levels of cytokines. These findings uncover oncogenic roles of LKB1 somatic mutations, and will aid in further understanding their contributions to cancer development and progression. |
dc.language.iso | eng |
dc.publisher | Nature Research |
dc.relation.ispartofseries | Communications Biology;3 |
dc.rights | Attribution 4.0 International |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ |
dc.source | Scientia |
dc.subject | Càncer - Aspectes genètics |
dc.subject | Regulació genètica |
dc.subject.mesh | Melanoma |
dc.subject.mesh | /genetics |
dc.subject.mesh | Gene Expression Regulation, Neoplastic |
dc.title | STK11 (LKB1) missense somatic mutant isoforms promote tumor growth, motility and inflammation |
dc.type | info:eu-repo/semantics/article |
dc.identifier.doi | 10.1038/s42003-020-1092-0 |
dc.subject.decs | regulación de la expresión génica neoplásica |
dc.subject.decs | melanoma |
dc.subject.decs | /genética |
dc.relation.publishversion | https://doi.org/10.1038/s42003-020-1092-0 |
dc.type.version | info:eu-repo/semantics/publishedVersion |
dc.audience | Professionals |
dc.contributor.organismes | Institut Català de la Salut |
dc.contributor.authoraffiliation | [Granado-Martínez P, Garcia-Ortega S, González-Sánchez E, McGrail K, Selgas R, Gil R, Recio JA] Grup de Recerca Biomèdica en Melanoma. Models Animals de Càncer, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Grueso J] Grup de Recerca Biomèdica en Melanoma. Models Animals de Càncer, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Naldaiz-Gastesi N] Grup de Recerca Biomèdica en Melanoma. Models Animals de Càncer, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Biodonostia, Neurosciences Area, Group of Neuromuscular Diseases, San Sebastian 20014, Spain. [Rhodes AC] Grup de Recerca Biomèdica en Melanoma. Models Animals de Càncer, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clínic of Barcelona, University of Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona 08036, Spain. [Hernandez-Losa J] Servei d’Anatomia Patològica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Ferrer B] Grup de Recerca Biomèdica en Melanoma. Models Animals de Càncer, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Servei d’Anatomia Patològica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Canals F] Proteomics Laboratory, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Villanueva J, Méndez O] Preclinical Research Program, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Muñoz-Couselo E] Grup de Recerca Biomèdica en Melanoma. Models Animals de Càncer, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Clinical Oncology Program, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain |
dc.identifier.pmid | 32647375 |
dc.identifier.wos | 000552080500009 |
dc.relation.projectid | info:eu-repo/grantAgreement/ES/PE2013-2016/PI14%2F00375 |
dc.relation.projectid | info:eu-repo/grantAgreement/ES/PE2013-2016/PI17%2F00043 |
dc.relation.projectid | info:eu-repo/grantAgreement/ES/PE2013-2016/AC16%2F00019 |
dc.rights.accessrights | info:eu-repo/semantics/openAccess |
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