Cellular signals integrate cell cycle and metabolic control in cancer

• Main Author: Akekawatchai C.
• Other Authors: Mahidol University
• Format: Book Chapter
• Published: 2023
• Subjects: Biochemistry, Genetics and Molecular Biology
• Online Access: https://repository.li.mahidol.ac.th/handle/123456789/82315

Growth factors are the small peptides that can promote growth, differentiation, and survival of most living cells. However, aberrant activation of receptor tyrosine kinases by GFs can generate oncogenic signals, resulting in oncogenic transformation. Accumulating evidence support a link between GF/RTK signaling through the major signaling pathways, Ras/Erk and PI3K/Akt, and cell cycle progression. In response to GF signaling, the quiescent cells in the G0 stage can re-enter the cell cycle and become the proliferative stage. While in the proliferative stage, tumor cells undergo profound changes in their metabolism to support biomass production and bioenergetic requirements. Accumulating data show that the cell cycle regulators, specifically cyclin D, cyclin B, Cdk2, Cdk4, and Cdk6, and anaphase-promoting complex/cyclosome (APC/C-Cdh1) play critical roles in modulating various metabolic pathways. These cell cycle regulators can regulate metabolic enzyme activities through post-translational mechanisms or the transcriptional factors that control the expression of the metabolic genes. This fine-tune control allows only the relevant metabolic pathways to be active in a particular phase of the cell cycle, thereby providing suitable amounts of biosynthetic precursors available during the proliferative stage. The imbalance of metabolites in each cell cycle phase can induce cell cycle arrest followed by p53-induced apoptosis.