In vivo Reprogramming of Cancer Metabolism by MYC

Abstract

The past few decades have welcomed tremendous advancements toward understanding the functional significance of altered metabolism during tumorigenesis. However, many conclusions drawn from studies of cancer cells in a dish (i.e., in vitro) have been put into question as multiple lines of evidence have demonstrated that the metabolism of cells can differ significantly from that of primary tumors (in vivo). This realization, along with the need to identify tissue-specific vulnerabilities of driver oncogenes, has led to an increased focus on oncogene-dependent metabolic programming in vivo. The oncogene c-MYC (MYC) is overexpressed in a wide variety of human cancers, and while its ability to alter cellular metabolism is well-established, translating the metabolic requirements, and vulnerabilities of MYC-driven cancers to the clinic has been hindered by disparate findings from in vitro and in vivo models. This review will provide an overview of the in vivo strategies, mechanisms, and conclusions generated thus far by studying MYC's regulation of metabolism in various cancer models.

Oncogene Regulated Release of Extracellular Vesicles

“…MCF10A cells which overexpress MYC demonstrated the greatest number of EVs and EV biomass released. MYC is a pleiotropic transcription factor that alters transcription of many genes involved in a wide variety of processes, including but not limited to, proliferation, apoptosis and metabolism (Meyer, Penn, 2008, Camarda, Williams & Goga, 2017, Gabay, Li & Felsher, 2014. The MYC oncogene is also overexpressed in many of the most aggressive types of human cancers, such as lymphoma, receptor triple negative breast cancer, and liver cancer (Lin et al, 2012, Horiuchi, Anderton & Goga, 2014.…”

Adipocyte JAK2 mediates aging-associated metabolic liver disease and progression to hepatocellular carcinoma

“…How insulin resistant adipocytes promote oncogenesis is unknown, but a role for fatty acid receptors has been proposed (53). In addition, metabolic re-programming in HCC is mediated by the master oncogene Myc (54) and MYC levels themselves are induced by cellular exposure to fatty acids (55). Interestingly, a single bolus of GH increased hepatic Myc expression within one hour of administration (56).…”

GLUT1 inhibition blocks growth of RB1-positive Triple Negative Breast Cancer

“…Mutations that activate oncogenes or inactivate tumor suppressors can significantly affect activities of metabolic enzymes and have a key role in aerobic glycolysis of cancer 23,24,[60][61][62] . Phosphatidylinositol 3'-kinase (PI3K) 63 , phosphatase and tensin homolog (PTEN) 64 , Myc 65,66 and p53 67 can all impact cellular glucose metabolism. Here, we discovered the significant correlation between RB1-E2F Targets pathway and OXPHOS in both cell lines and TNBC primary tumors.…”