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dc.contributor.authorMontero-Calle, Ana Maria 
dc.contributor.authorGómez de Cedrón, Marta
dc.contributor.authorQuijada-Freire, Adriana
dc.contributor.authorSolís-Fernández, Guillermo
dc.contributor.authorLopez-Alonso, Victoria 
dc.contributor.authorEspinosa-Salinas, Isabel
dc.contributor.authorPeláez-García, Alberto
dc.contributor.authorFernández-Aceñero, María Jesús
dc.contributor.authorRamírez de Molina, Ana
dc.contributor.authorBarderas Manchado, Rodrigo
dc.identifier.citationFront Oncol. 2022 Jul 25;12:903033.es_ES
dc.description.abstractApproximately 25% of colorectal cancer (CRC) patients experience systemic metastases, with the most frequent target organs being the liver and lung. Metabolic reprogramming has been recognized as one of the hallmarks of cancer. Here, metabolic and functional differences between two CRC cells with different metastatic organotropisms (metastatic KM12SM CRC cells to the liver and KM12L4a to the lung when injected in the spleen and in the tail vein of mice) were analysed in comparison to their parental non-metastatic isogenic KM12C cells, for a subsequent investigation of identified metabolic targets in CRC patients. Meta-analysis from proteomic and transcriptomic data deposited in databases, qPCR, WB, in vitro cell-based assays, and in vivo experiments were used to survey for metabolic alterations contributing to their different organotropism and for the subsequent analysis of identified metabolic markers in CRC patients. Although no changes in cell proliferation were observed between metastatic cells, KM12SM cells were highly dependent on oxidative phosphorylation at mitochondria, whereas KM12L4a cells were characterized by being more energetically efficient with lower basal respiration levels and a better redox management. Lipid metabolism-related targets were found altered in both cell lines, including LDLR, CD36, FABP4, SCD, AGPAT1, and FASN, which were also associated with the prognosis of CRC patients. Moreover, CD36 association with lung metastatic tropism of CRC cells was validated in vivo. Altogether, our results suggest that LDLR, CD36, FABP4, SCD, FASN, LPL, and APOA1 metabolic targets are associated with CRC metastatic tropism to the liver or lung. These features exemplify specific metabolic adaptations for invasive cancer cells which stem at the primary tumour.es_ES
dc.description.sponsorshipThis work was supported by grants cofounded by Fondo Europeo de Desarrollo Regional -FEDER- PI17CIII/00045 and PI20CIII/00019 from the AES-ISCIII program to RB from the Instituto de Salud Carlos III (ISCIII) and grants from Spanish Ministry of Science (Plan Nacional I+D+i PID2019-110183RBC21), Regional Government of Community of Madrid (P2018/BAA-4343-ALIBIRD2020-CM, and Y2020/BIO-6350), and Ramón Areces Foundation (CIVP19A5937) to AR. AM-C FPU predoctoral contract is supported by the Spanish Ministerio de Educació n, Cultura y Deporte. AQ-F acknowledges Comunidad de Madrid for the Garantıa Juvenil PEJD-2017-RE/BMD-3394 contract. GS-F is a recipient of a predoctoral contract (grant number 1193818N) supported by the Flanders Research Foundation (FWO).es_ES
dc.publisherFrontiers Media es_ES
dc.relation.isversionofPublisher's versiones_ES
dc.subjectCRC (colorectal cancer)es_ES
dc.subjectMetabolic reprograminges_ES
dc.subjectTropism of metastasises_ES
dc.subjectFatty acids (FA)es_ES
dc.titleMetabolic Reprogramming Helps to Define Different Metastatic Tropisms in Colorectal Canceres_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.contributor.funderUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) es_ES
dc.contributor.funderInstituto de Salud Carlos III es_ES
dc.contributor.funderMinisterio de Ciencia (España) es_ES
dc.contributor.funderPlan Nacional de I+D+i (España) es_ES
dc.contributor.funderComunidad de Madrid (España) es_ES
dc.contributor.funderFundación Ramón Areces es_ES
dc.contributor.funderMinisterio de Educación, Cultura y Deporte (España) es_ES
dc.contributor.funderResearch Foundation - Flanders es_ES
dc.identifier.journalFrontiers in oncologyes_ES
dc.repisalud.centroISCIII::Unidad Funcional de Investigación de Enfermedades Crónicas (UFIEC)es_ES

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Atribución-NoComercial-CompartirIgual 4.0 Internacional
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