Metabolism and cancer

Summary

The Metabolism and Cancer group includes Doctors George Thomas, Sara Kozma, Albert Tauler and Antonio Gentilella. The program focuses on the kinase signalling of the mammalian target of rapamycin complex 1 (mTORC1) and its main metabolic cascade responses, including ribosome biogenesis, control of translation, metabolic reprogramming, autophagy, lysosomal transport and cell proliferation. The group’s aim is to unveil metabolic vulnerabilities in cancer to promote new clinical treatments, using colorectal cancer (CRC) and other c-MYC driven tumor models and by interacting with oncologists and pharmaceutical companies.

415 Publications

Strategic lines

Selected Publications

Lluch A, Veiga SR, Latorre J, Moreno Navarrete JM, Bonifaci N, Nguyen VD, Zhou Y, Horing M, Liebisch G, Olkkonen VM, Llobet Navas D, Thomas G, Rodriguez Barrueco R, Fernández Real JM, Kozma SC, Ortega FJ. A compound directed against S6K1 hampers fat mass expansion and mitigates diet-induced hepatosteatosis. JCI Insight. 2022;7(14):doi:10.1172/jci.insight.150461.

Almacellas E, Garcia Cajide M, Tauler A, Mauvezin C. Analysis of Autophagic Vesicles in Mitotic Cells. Methods Mol Biol. 2022;2445127-137. doi:10.1007/978-1-0716-2071-7_9.

Pons C, Almacellas E, Tauler A, Mauvezin C. Detection of Nuclear Biomarkers for Chromosomal Instability. Methods Mol Biol. 2022;2445117-125. doi:10.1007/978-1-0716-2071-7_8.

Domostegui A, Peddigari S, Mercer CA, Iannizzotto F, Rodriguez ML, Garcia Cajide M, Amador V, Diepstraten ST, Kelly GL, Salazar R, Kozma SC, Kusnadi EP, Kang J, Gentilella A, Pearson RB, Thomas G, Pelletier J.
Impaired ribosome biogenesis checkpoint activation induces p53-dependent MCL-1 degradation and MYC-driven lymphoma death. Blood. 2021;137(24):3351-3364. doi:10.1182/blood.2020007452.

Almacellas E, Pelletier J, Day C, Ambrosio S, Tauler A, Mauvezin C. Lysosomal degradation ensures accurate chromosomal segregation to prevent chromosomal instability. Autophagy. 2021;17(3):796-813. doi:10.1080/15548627.2020.1764727.

Selected Projects

AEC21004. Overcoming resistance to therapy in Colorectal Cancer by attacking the 40S-LARP1-5’TOPs anabolic reservoir. Asociación Española Contra el Cáncer (AECC). Budget: 165.000€. 2021-2026. PI: Gentilella, Antonio, Pedro Fuentes .
20PSJ024. Overcoming resistance to therapy in Colorectal Cancer by attacking the 40S-LARP1-5’TOPs anabolic reservoir. Asociación Española Contra el Cáncer (AECC). Budget: 150.000€. 2020-2025. PI: Gentilella, Antonio.
19MEC009. AYUDAS PARA CONTRATOS PREDOCTORALES PARA LA FORMACIÓN DE DOCTORES 2018. Ministerio de Ciencia e Innovación. Budget: 88.250€. 2019-2023. PI: Gentilella, Antonio.
PID2021-122125NB-I00. Role of the 40S-LARP1 complex for the maintenance of tumor anabolic potential in colorectal cancer. Ministerio de Ciencie y Innovacion. Budget: 256.000€. 2022-2025. PI: Antonio Gentilella.
PID2022-141127OA-I00. Bloqueo de la biogénesis ribisomal y la inflamación celular autónoma como nueva terapia de diferenciación en el cáncer colorectal. Ministerio de Ciencia e Innovación . Budget: 260.000€. 2023-2026. PI: Joffrey Pelletier.

More Information

Dr Thomas and Dr Kozma are renowned for their discoveries related to the mTORC1/S6K1/4E-BP1 signalling pathway, having obtained FDA approval for the use of rapamycin in different types of cancer and to launch clinical trials based on the use of specific mTOR dual inhibitors.

Dr Tauler has worked extensively on the glycolytic pathway and its control through mitogenic signals. Some of his studies on PF2K bifunctionality are included in leading Biochemistry textbooks