Colorectal Cancer and Metabolism

Abstract

Purpose of Review-Metabolic reprogramming is essential for the rapid proliferation of cancer cells and is thus recognized as a hallmark of cancer. In this review, we will discuss the etiologies and effects of metabolic reprogramming in colorectal cancer. Recent Findings-Changes in cellular metabolism may precede the acquisition of driver mutations ultimately leading to colonocyte transformation. Oncogenic mutations and loss of tumor suppressor genes further reprogram CRC cells to upregulate glycolysis, glutaminolysis, onecarbon metabolism, and fatty acid synthesis. These metabolic changes are not uniform throughout tumors, as subpopulations of tumor cells may rely on different pathways to adapt to nutrient availability in the local tumor microenvironment. Finally, metabolic cross-communication between stromal cells, immune cells, and the gut microbiota enable CRC growth, invasion, and metastasis. Summary-Altered cellular metabolism occurs in CRC at multiple levels, including in the cells that make up the bulk of CRC tumors, cancer stem cells, the tumor microenvironment, and hostmicrobiome interactions. This knowledge may inform the development of improved screening and therapeutics for CRC.

Elucidating the Reprograming of Colorectal Cancer Metabolism Using Genome-Scale Metabolic Modeling

“…We also found FASN, ACLY, ACACA, and SCD are significantly up-regulated, which indicated an increased fatty acid biosynthesis. It is clinically well-known that fatty acid synthesis is increased in colorectal cancer (25), and this could help the cancer cell to produce lipid metabolites crucial to cell membranes, cell signaling, post-translational modifications of proteins, neutralization of toxic reactive oxygen species, and energy storage (26). In addition, we found GLS2 is also significantly up-regulated, which indicated an increased uptake of glutamine and suggested increased glutaminolysis in the cancer cells.…”

Targeting Metabolism in Cancer Cells and the Tumour Microenvironment for Cancer Therapy

“…), which are channelled into biosynthesis via the core metabolic pathways of glycolysis, the tricarboxylic acid (TCA) cycle, the PPP, and non-essential amino acid synthesis, which is followed by subsequent ATP-dependent processes to produce complex biomolecules ( Figure 1 ). Many cancers are known to upregulate glucose consumption, and the classical Warburg phenotype has been reported in a variety of tumour types [ 9 , 10 , 11 ]. However, a majority of tumours still retain oxidative capacity to produce ATP via OXPHOS [ 4 , 12 , 13 , 14 , 15 ].…”

Targeting Altered Energy Metabolism in Colorectal Cancer: Oncogenic Reprogramming, the Central Role of the TCA Cycle and Therapeutic Opportunities

“…Phosphatidylinositol 3-kinases (PI3Ks) are a family of enzymes, which are important for intracellular signal transduction. They are activated by receptor tyrosine kinases (RTKs) and G protein-coupled receptors after binding growth factors like epidermal growth factor (EGF) or by oncogenes like RAS [ 76 , 77 ]. While growth factors interact with the regulatory subunit p85, RAS directly activates the catalytic subunit p110 of PI3K [ 77 ].…”