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dc.contributor.author | Tummala, Krishna S | |
dc.contributor.author | Brandt, Marta | |
dc.contributor.author | Teijeiro, Ana | |
dc.contributor.author | Graña Castro, Osvaldo | |
dc.contributor.author | Schwabe, Robert F | |
dc.contributor.author | Perna, Cristian | |
dc.contributor.author | Djouder, Nabil | |
dc.date.accessioned | 2019-02-25T12:33:43Z | |
dc.date.available | 2019-02-25T12:33:43Z | |
dc.date.issued | 2017-04-19 | |
dc.identifier.citation | Cell Rep. 2017;19(3):584-600. | es_ES |
dc.identifier.issn | 22111247 | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/7231 | |
dc.description.abstract | Hepatocellular carcinoma (HCC) is an aggressive primary liver cancer. However, its origin remains a debated question. Using human data and various hepatocarcinogenesis mouse models, we show that, in early stages, transformed hepatocytes, independent of their proliferation status, activate hepatic progenitor cell (HPC) expansion. Genetic lineage tracing of HPCs and hepatocytes reveals that, in all models, HCC originates from hepatocytes. However, whereas in various models tumors do not emanate from HPCs, tracking of progenitors in a model mimicking human hepatocarcinogenesis indicates that HPCs can generate benign lesions (regenerative nodules and adenomas) and aggressive HCCs. Mechanistically, galectin-3 and α-ketoglutarate paracrine signals emanating from oncogene-expressing hepatocytes instruct HPCs toward HCCs. α-Ketoglutarate preserves an HPC undifferentiated state, and galectin-3 maintains HPC stemness, expansion, and aggressiveness. Pharmacological or genetic blockage of galectin-3 reduces HCC, and its expression in human HCC correlates with poor survival. Our findings may have clinical implications for liver regeneration and HCC therapy. | es_ES |
dc.description.sponsorship | We thank G. Yeoh and N. Tirnitz-Parker for sharing BMOL cells and X. Sole for helping with statistics. We thank E. Wagner for critical reading of this manu- script. M.B. is a recipient of a La Caixa PhD fellowship. N.D. is a recipient of the Spanish Ramon y Cajal fellowship. This work was supported by grants from the Spanish Ministry of Economy and Competitiveness (SAF2013- 46089-R) and AICR-UK (11-0242) (all to N.D.) | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Elsevier | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | DNA damage | es_ES |
dc.subject | HCC | es_ES |
dc.subject | NAD(+) | es_ES |
dc.subject | Adenomas | es_ES |
dc.subject | Galectin-3 | es_ES |
dc.subject | Hepatic progenitor cells | es_ES |
dc.subject | Hepatocytes | es_ES |
dc.subject | Lineage tracking | es_ES |
dc.subject | Regenerative nodules | es_ES |
dc.subject | α-ketoglutarate | es_ES |
dc.subject.mesh | Animals | es_ES |
dc.subject.mesh | Carcinogenesis | es_ES |
dc.subject.mesh | Carcinoma, Hepatocellular | es_ES |
dc.subject.mesh | Cell Differentiation | es_ES |
dc.subject.mesh | Galectin 3 | es_ES |
dc.subject.mesh | Hepatocytes | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | Ketoglutaric Acids | es_ES |
dc.subject.mesh | Liver Neoplasms | es_ES |
dc.subject.mesh | Mice, Transgenic | es_ES |
dc.subject.mesh | Neoplasm Invasiveness | es_ES |
dc.subject.mesh | Stem Cells | es_ES |
dc.title | Hepatocellular Carcinomas Originate Predominantly from Hepatocytes and Benign Lesions from Hepatic Progenitor Cells | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 28423321 | es_ES |
dc.format.volume | 19 | es_ES |
dc.format.number | 3 | es_ES |
dc.format.page | 584-600 | es_ES |
dc.identifier.doi | 10.1016/j.celrep.2017.03.059 | es_ES |
dc.contributor.funder | Fundación La Caixa | |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 2211-1247 | es_ES |
dc.relation.publisherversion | https://doi.org/10.1016/j.celrep.2017.03.059. | es_ES |
dc.identifier.journal | Cell reports | es_ES |
dc.repisalud.institucion | CNIO | es_ES |
dc.repisalud.orgCNIO | CNIO::Grupos de investigación::Grupo de Factores de Crecimiento, Nutrientes y Cáncer | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SAF2013-46089-R | es_ES |
dc.rights.accessRights | open access | es_ES |