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dc.contributor.authorRuiz de Garibay, Gorka
dc.contributor.authorHerranz, Carmen
dc.contributor.authorLlorente, Alicia
dc.contributor.authorBoni, Jacopo
dc.contributor.authorSerra- Musach, Jordi
dc.contributor.authorMateo, Francesca
dc.contributor.authorAguilar, Helena
dc.contributor.authorGómez-Baldó, Laia
dc.contributor.authorPetit, Anna
dc.contributor.authorVidal, August
dc.contributor.authorCliment, Fina
dc.contributor.authorHernández-Losa, Javier
dc.contributor.authorCordero, Álex
dc.contributor.authorGonzález- Suárez, Eva
dc.contributor.authorSánchez-Mut, José Vicente
dc.contributor.authorEsteller, Manel
dc.contributor.authorLlatjós, Roger
dc.contributor.authorVarela, Mar
dc.contributor.authorLópez Fernández de Villaverde, José Ignacio ORCID
dc.contributor.authorGarcía, Nadia
dc.contributor.authorExtremera, Ana I.
dc.contributor.authorGumà, Anna
dc.contributor.authorOrtega, Raúl
dc.contributor.authorPlà, María Jesús
dc.contributor.authorFernández, Adela
dc.contributor.authorPernas, Sònia
dc.contributor.authorFalo, Catalina
dc.contributor.authorMorilla, Idoia
dc.contributor.authorCampos, Miriam
dc.contributor.authorGil, Miguel
dc.contributor.authorRomán, Antonio
dc.contributor.authorMolina-Molina, María
dc.contributor.authorUssetti, Piedad
dc.contributor.authorLaporta, Rosalía
dc.contributor.authorValenzuela, Claudia
dc.contributor.authorAncochea, Julio
dc.contributor.authorXaubet, Antoni
dc.contributor.authorCasanova, Álvaro
dc.contributor.authorPujana, Miguel Angel
dc.date.accessioned2016-04-11T11:02:07Z
dc.date.available2016-04-11T11:02:07Z
dc.date.issued2015-07-07
dc.identifier.citationPLOS ONE 10(7) : (2015) // Article ID e0132546es
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/10810/17872
dc.description.abstractLymphangioleiomyomatosis (LAM) is a rare lung-metastasizing neoplasm caused by the proliferation of smooth muscle-like cells that commonly carry loss-of-function mutations in either the tuberous sclerosis complex 1 or 2 (TSC1 or TSC2) genes. While allosteric inhibition of the mechanistic target of rapamycin (mTOR) has shown substantial clinical benefit, complementary therapies are required to improve response and/or to treat specific patients. However, there is a lack of LAM biomarkers that could potentially be used to monitor the disease and to develop other targeted therapies. We hypothesized that the mediators of cancer metastasis to lung, particularly in breast cancer, also play a relevant role in LAM. Analyses across independent breast cancer datasets revealed associations between low TSC1/2 expression, altered mTOR complex 1 (mTORC1) pathway signaling, and metastasis to lung. Subsequently, immunohistochemical analyses of 23 LAM lesions revealed positivity in all cases for the lung metastasis mediators fascin 1 (FSCN1) and inhibitor of DNA binding 1 (ID1). Moreover, assessment of breast cancer stem or luminal progenitor cell biomarkers showed positivity in most LAM tissue for the aldehyde dehydrogenase 1 (ALDH1), integrin-beta 3 (ITGB3/CD61), and/or the sex-determining region Y-box 9 (SOX9) proteins. The immunohistochemical analyses also provided evidence of heterogeneity between and within LAM cases. The analysis of Tsc2-deficient cells revealed relative over-expression of FSCN1 and ID1; however, Tsc2-deficient cells did not show higher sensitivity to ID1-based cancer inhibitors. Collectively, the results of this study reveal novel LAM biomarkers linked to breast cancer metastasis to lung and to cell stemness, which in turn might guide the assessment of additional or complementary therapeutic opportunities for LAM.es
dc.description.sponsorshipThis work was funded by the Government of Catalonia grant SGR 2014-364, the "Red Tematica de Investigacion Colaborativa en Cancer" grant RD12/0036/0008, the Telemaraton 2014 "Todos Somos Raros, Todos Somos Unicos" grant P35, the Spanish Ministry of Health "Instituto de Salud Carlos III Fondo de Investigacion Sanitaria" grant PI12/01528, and a Spanish Society of Pneumology and Thoracic Surgery (Sociedad Espanola de Neumologia y Cirugia Toracica, SEPAR) grant for 2012. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.es
dc.language.isoenges
dc.publisherPublic Library Sciencees
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.subjecttouberous sclerosis complexes
dc.subjectsporadic pulmonary lymphangioleiomyomatosises
dc.subjecthuman breast canceres
dc.subjectductal carcinomaes
dc.subjectself-renewales
dc.subjectID proteinses
dc.subjectgene TSC2es
dc.subjectexpressiones
dc.subjecttransplantationes
dc.subjectactivationes
dc.titleLymphangioleiomyomatosis Biomarkers Linked to Lung Metastatic Potential and Cell Stemnesses
dc.typeinfo:eu-repo/semantics/articlees
dc.rights.holder© 2015 Ruiz de Garibay et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedes
dc.relation.publisherversionhttp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0132546#abstract0es
dc.identifier.doi10.1371/journal.pone.0132546
dc.departamentoesEspecialidades médico-quirúrgicases_ES
dc.departamentoeuMedikuntza eta kirurgia espezialitateakes_ES
dc.subject.categoriaAGRICULTURAL AND BIOLOGICAL SCIENCES
dc.subject.categoriaMEDICINE
dc.subject.categoriaBIOCHEMISTRY AND MOLECULAR BIOLOGY


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