MYC and metabolism on the path to cancer

Abstract

The MYC proto-oncogene is frequently deregulated in human cancers, activating genetic programs that orchestrate biological processes to promote growth and proliferation. Altered metabolism characterized by heightened nutrients uptake, enhanced glycolysis and glutaminolysis and elevated fatty acid and nucleotide synthesis is the hallmark of MYC-driven cancer. Recent evidence strongly suggests that Myc-dependent metabolic reprogramming is critical for tumorigenesis, which could be attenuated by targeting specific metabolic pathways using small drug-like molecules. Understanding the complexity of MYC-mediated metabolic re-wiring in cancers as well as how MYC cooperates with other metabolic drivers such as mammalian target of rapamycin (mTOR) will provide translational opportunities for cancer therapy.

Myc/Mycn-mediated glycolysis enhances mouse spermatogonial stem cell self-renewal

“…Because of the possible correlation between "stemness" and metabolism, we analyzed the glycolytic activity of GS cells. The metabolic function of Myc is context-dependent; Myc is implicated in glycolysis but is also involved in mitochondrial biogenesis and oxygen consumption (Hsieh et al 2015). Therefore, we analyzed the glycolytic activity of GS cells and found that Myc double-knockout GS cells have reduced glycolytic activity (Fig.…”

“…Because Myc is involved in glycolysis as well as mitochondrial biogenesis (Hsieh et al 2015), we reasoned that SSCs and progenitors balance these metabolic pathways differently, which might disturb the frequency of self-renewal division. We used a Seahorse extracellular flux analyzer to measure two metabolic parameters: the oxygen consumption rate (OCR) and extracellular acidification rate (ECAR).…”

The Role of PGC1α in Cancer Metabolism and its Therapeutic Implications

“…MYC/PGC1a axis in pancreatic ductal adenocarcinoma MYC-driven metabolic reprogramming is critical for cancer cell survival and proliferation (77,78). Most recently, MYC has been confirmed to be a direct regulator of PGC1a in pancreatic ductal adenocarcinoma (PDAC; ref.…”

Methylglyoxal suppresses human colon cancer cell lines and tumor growth in a mouse model by impairing glycolytic metabolism of cancer cells associated with down-regulation of c-Myc expression

“…19 c-Myc is involved in regulating glycolytic genes and thus enhancing glycolysis. 21 Its overexpression has the effect of addicting cancer cells to glucose or glutamine, without which the cells die. 22 Emerging evidence suggests that cancer is a metabolic disease, and what has been learned about the Warburg effect indicates that malignant cells rely on glycolysis as their major energy source.…”