Cancer Cells Tune the Signaling Pathways to Empower de Novo Synthesis of Nucleotides
Open Access
- 16 May 2019
- Vol. 11 (5), 688
- https://doi.org/10.3390/cancers11050688
Abstract
Cancer cells exhibit a dynamic metabolic landscape and require a sufficient supply of nucleotides and other macromolecules to grow and proliferate. To meet the metabolic requirements for cell growth, cancer cells must stimulate de novo nucleotide synthesis to obtain adequate nucleotide pools to support nucleic acid and protein synthesis along with energy preservation, signaling activity, glycosylation mechanisms, and cytoskeletal function. Both oncogenes and tumor suppressors have recently been identified as key molecular determinants for de novo nucleotide synthesis that contribute to the maintenance of homeostasis and the proliferation of cancer cells. Inactivation of tumor suppressors such as TP53 and LKB1 and hyperactivation of the mTOR pathway and of oncogenes such as MYC, RAS, and AKT have been shown to fuel nucleotide synthesis in tumor cells. The molecular mechanisms by which these signaling hubs influence metabolism, especially the metabolic pathways for nucleotide synthesis, continue to emerge. Here, we focus on the current understanding of the molecular mechanisms by which oncogenes and tumor suppressors modulate nucleotide synthesis in cancer cells and, based on these insights, discuss potential strategies to target cancer cell proliferation.Funding Information
- National Cancer Institute (R00CA194192)
- LAM Foundation (Career development award)
This publication has 128 references indexed in Scilit:
- Oncogenic Kras Maintains Pancreatic Tumors through Regulation of Anabolic Glucose MetabolismCell, 2012
- MYC on the Path to CancerCell, 2012
- Hallmarks of Cancer: The Next GenerationCell, 2011
- Oncogenic K‐Ras decouples glucose and glutamine metabolism to support cancer cell growthMolecular Systems Biology, 2011
- A Gene Expression Signature Associated with “K-Ras Addiction” Reveals Regulators of EMT and Tumor Cell SurvivalCancer Cell, 2009
- Enzymology of Purine and Pyrimidine Antimetabolites Used in the Treatment of CancerChemical Reviews, 2009
- The molecular determinants of de novo nucleotide biosynthesis in cancer cellsCurrent Opinion in Genetics & Development, 2009
- Mutations of the BRAF gene in human cancerNature, 2002
- Negative Regulation of PKB/Akt-Dependent Cell Survival by the Tumor Suppressor PTENCell, 1998
- Fluorinated Pyrimidines, A New Class of Tumour-Inhibitory CompoundsNature, 1957