Next Article in Journal
Fibroblast-Mediated Immunoregulation of Macrophage Function Is Maintained after Irradiation
Previous Article in Journal
Pretreatment Cancer-Related Cognitive Impairment—Mechanisms and Outlook
Previous Article in Special Issue
The Non-Essential Amino Acid Cysteine Becomes Essential for Tumor Proliferation and Survival
Article Menu
Issue 5 (May) cover image

Export Article

Open AccessReview

Cancer Cells Tune the Signaling Pathways to Empower de Novo Synthesis of Nucleotides

1,†, 1,†, 1,† and 1,2,*
1
Department of Biochemistry and Molecular Genetics, Northwestern University, Chicago, IL 60611, USA
2
Robert H. Lurie Cancer Center, Northwestern University, Chicago, IL 60611, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to the work.
Cancers 2019, 11(5), 688; https://doi.org/10.3390/cancers11050688
Received: 22 April 2019 / Revised: 13 May 2019 / Accepted: 15 May 2019 / Published: 17 May 2019
(This article belongs to the Special Issue Metabolic Reprogramming and Vulnerabilities in Cancer)
  |  
PDF [1521 KB, uploaded 17 May 2019]
  |     |  

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. View Full-Text
Keywords: de novo nucleotide synthesis; oncogenes; tumor suppressors; mTORC1; MYC; RAS; AKT; cancer metabolism; short term and long-term regulation; metabolic vulnerability de novo nucleotide synthesis; oncogenes; tumor suppressors; mTORC1; MYC; RAS; AKT; cancer metabolism; short term and long-term regulation; metabolic vulnerability
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Villa, E.; Ali, E.S.; Sahu, U.; Ben-Sahra, I. Cancer Cells Tune the Signaling Pathways to Empower de Novo Synthesis of Nucleotides. Cancers 2019, 11, 688.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Cancers EISSN 2072-6694 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top