Ibec Seminar. Dr. Le Cam
The p53 pathway and metabolism: implications in normal tissue homeostasis, aging and cancer progression
Dr. Le Cam , Montpellier Cancer Research Institute (IRCM)
Mutation of the TP53 gene is the most frequent genetic alteration in human cancers. Tumor suppressive functions of p53 have been linked to its ability to control cell division, cell death and cellular senescence. However growing evidence indicates that the metabolic functions of p53 play important roles in cancer progression. Our team has been studying the metabolic functions of the p53 pathway for many years and highlighted previously unknown functions of several key components of this molecular cascade in pyruvate, amino-acid, and nucleotide metabolism. Beyond cancer development, I will illustrate how deregulation of these metabolic networks impacts on normal physiological responses in the liver, contributes to cancer development and leads to inborn metabolic disorders.
Relevant publications:
1- Riscal R. et al (2016) Chromatin-bound MDM2 regulates serine metabolism and redox homeostasis independently of p53. Mol. Cell. Jun 16;62(6):890-902.
2- Arena et al. Mitochondrial MDM2 regulates respiratory complex I activity independently of p53. Mol Cell 2018
3- Cissé et al. Targeting MDM2-dependent serine metabolism as a new therapeutic strategy for liposarcoma. Sci Trans Med 2020
4- Lacroix et al. The multifunctional protein E4F1 links p53 to lipid metabolism in adipocytes. Nat Comms 2021
5- Di Michele et al. E4F1 coordinates pyruvate metabolism and the activity of the Elongator Complex to ensure protein translation fidelity. Nat Comms 2025
Dr. Le Cam earned his Pharmacy thesis and his PhD in Science from Montpellier University (France) in 1999. From 1999 to 2004, he spent four years as a postdoctoral fellow in Professor Sicinski’s laboratory at the Dana-Farber Cancer Institute in Boston (USA), where he studied cell cycle and mouse genetics. He then joined the French National Institute of Health and Medical Research (INSERM) as a researcher at the Institute of Molecular Genetics of Montpellier in Dr. Claude Sardet’s laboratory. In 2008, he became a group leader at the Montpellier Cancer Research Institute (IRCM), where he was appointed deputy director in 2022. His team investigates the metabolic functions of p53, the most frequently mutated tumor suppressor across many cancer types, and how their deregulation impinges on metabolic disorders, aging and cancer progression.
