TRANSCRIPTOMIC AND METABOLIC PATHWAY ANALYSIS REVEALS THE MUTATED GENES P53 AND TP53 AND THEIR ROLE IN DIFFERENT TYPES OF CANCER

Somatic TP53 gene mutations are common in different cancers, occurring in almost half of ovarian tumors. These mutations result in the p53 protein, which is less able to control cell proliferation. In particular, it failed to induce apoptosis in cells with mutated or damaged DNA. An inherited TP53 mutation is known as Li-Fraumeni syndrome. Li-Fraumeni syndrome is a rare genetic disorder that can increase the risk of certain types of cancer. These cancers include breast cancer, bone cancer, leukemia, and soft tissue cancer, also known as sarcomas. Mutations (changes) in the p53 gene can cause cancer cells to grow and spread throughout the body. These changes have been found in a genetic disorder known as Li-Fraumeni syndrome and in many types of cancer. The p53 gene is a tumor suppressor gene. Also called TP53 gene and tumor protein p53 gene. P53 mutations are associated with breast, colorectal, liver, lung, and ovarian cancers. Environ Health Perspect. Frequent p53 mutations (mutp53) not only end tumor suppressor capacities but confer various gain-of-function (GOF) activities that impact molecules and pathways now regarded as central for tumor development and progression. Although the complete impact of GOF is still far from being fully understood, the effects on proliferation, migration, metabolic reprogramming, and immune evasion, among others, certainly constitute major driving forces for human tumors harboring them. I In particular, the increased lipogenic activity through the mevalonate pathway (MVA) and the alteration of metabolic homeostasis due to interactions between mutp53 and AMP-activated protein kinase (AMPK) and Sterol regulatory element-binding protein 1 (SREBP1) that impact anabolic pathways and favor metabolic reprogramming. We address, in detail, the impact of mutp53 over metabolic reprogramming and the Warburg effect observed in cancer cells as a consequence, not only of loss-of-function of p53, but rather as an effect of GOF that is crucial for the imbalance between glycolysis and oxidative phosphorylation