دورية أكاديمية

Metabolic Reprogramming Helps to Define Different Metastatic Tropisms in Colorectal Cancer

التفاصيل البيبلوغرافية
العنوان: Metabolic Reprogramming Helps to Define Different Metastatic Tropisms in Colorectal Cancer
المؤلفون: Montero-Calle, Ana Maria, Gómez de Cedrón, Marta, Quijada-Freire, Adriana, Solís-Fernández, Guillermo, Lopez-Alonso, Victoria, Espinosa-Salinas, Isabel, Peláez-García, Alberto, Fernández-Aceñero, María Jesús, Ramírez de Molina, Ana, Barderas Manchado, Rodrigo
المساهمون: Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), Instituto de Salud Carlos III, Ministerio de Ciencia (España), Plan Nacional de I+D+i (España), Comunidad de Madrid (España), Fundación Ramón Areces, Ministerio de Educación, Cultura y Deporte (España), Research Foundation - Flanders
بيانات النشر: Frontiers Media
سنة النشر: 2022
المجموعة: REPISALUD (REPositorio Institucional en SALUD del Instituto de Salud Carlos III - ISCIII)
مصطلحات موضوعية: CRC (colorectal cancer), Metabolic reprograming, Tropism of metastasis, Obesity, Fatty acids (FA), Organotropism
الوصف: Approximately 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. ; This 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 ...
نوع الوثيقة: article in journal/newspaper
اللغة: English
تدمد: 2234-943X
العلاقة: Publisher's version; https://doi.org/10.3389/fonc.2022.903033Test; info:eu-repo/grantAgreement/ES/PID2019-110183RBC21; info:eu-repo/grantAgreement/ES/PI17CIII/00045; info:eu-repo/grantAgreement/ES/PI20CIII/00019; Front Oncol. 2022 Jul 25;12:903033.; http://hdl.handle.net/20.500.12105/15011Test; Frontiers in oncology
DOI: 10.3389/fonc.2022.903033
الإتاحة: https://doi.org/20.500.12105/15011Test
https://doi.org/10.3389/fonc.2022.903033Test
https://hdl.handle.net/20.500.12105/15011Test
حقوق: http://creativecommons.org/licenses/by/4.0Test/ ; Atribución-NoComercial-CompartirIgual 4.0 Internacional ; info:eu-repo/semantics/openAccess
رقم الانضمام: edsbas.5CE53E0C
قاعدة البيانات: BASE
الوصف
تدمد:2234943X
DOI:10.3389/fonc.2022.903033