The Crosstalk Between Signaling Pathways and Cancer Metabolism in Colorectal Cancer

Abstract

Colorectal cancer (CRC) is one of the most frequently diagnosed cancers worldwide. Metabolic reprogramming represents an important cancer hallmark in CRC. Reprogramming core metabolic pathways in cancer cells, such as glycolysis, glutaminolysis, oxidative phosphorylation, and lipid metabolism, is essential to increase energy production and biosynthesis of precursors required to support tumor initiation and progression. Accumulating evidence demonstrates that activation of oncogenes and loss of tumor suppressor genes regulate metabolic reprogramming through the downstream signaling pathways. Protein kinases, such as AKT and c-MYC, are the integral components that facilitate the crosstalk between signaling pathways and metabolic pathways in CRC. This review provides an insight into the crosstalk between signaling pathways and metabolic reprogramming in CRC. Targeting CRC metabolism could open a new avenue for developing CRC therapy by discovering metabolic inhibitors and repurposing protein kinase inhibitors/monoclonal antibodies.

Emerging roles of cystathionine β-synthase in various forms of cancer

“…This switch from external-signal-dependent to intrinsic/perpetual proliferative signaling is often the consequence of key oncogenic mutations of the cancer cell that induce specific growth suppressor pathways and/or delete various tumor suppressors. Classical pathways that are considered essential for cancer cell proliferation include the PI3K/Akt, the Ras/Erk, and the mTOR pathways [ [287] , [288] , [289] , [290] , [291] ].…”

“…All of these actions result in increased PIP 3 levels. When PI3K/Akt is activated, the result is the activation of both proliferative and cytoprotective downstream pathways [ [287] , [288] , [289] , [290] , [291] ]. Exogenous H 2 S or polysulfide administration can, indeed, stimulate the Akt pathway in cancer cells – as shown, for instance in colon cancer cells [ 90 ] and neuroblastoma cells [ 298 , 299 ], multiple myeloma cells [ 128 ], hepatocellular carcinoma cells [ 129 , 300 ] and thyroid carcinoma cells [ 117 ].…”

Recent advances in understanding the metabolic plasticity of ovarian cancer: A systematic review

“…demonstrated that the (epi)genetic program influences metabolic choices of different cell types during the process of tumorigenesis by dynamically controlling glycolysis and OXPHOS activities [ 67 ] (“C”, “D”, and “E” in Figure 3 ). Furthermore, oncogenic mutations, such as amplification and increased oncogene expression, and tumor suppressor deletions (e.g., c-Myc, K-Ras, mutant p53, cyclin D1, HIF-1α, and the WNT/β-catenin signaling pathway) contribute to tumor metabolic reprogramming [ 68 , 69 ]. Oncogenic signaling pathways, such as phosphoinositide 3-kinase (PI3K)/AKT, Myc, and the Hippo pathway mediated upregulation and hyperactivation of metabolism-related genes [ 70 ].…”

Lipid Metabolism Interplay in CRC—An Update

“…First, we are focusing on epithelial cancer cells and their altered sources of intracellular fatty acid pools. We outline a functional and metabolic pathway-centric description, integrate underlying molecular concepts, leaving out driver mutations, transcriptional regulation (comprehensively reviewed elsewhere [ 23 ]) and briefly cover highly complex interactions of microbiota with the intestinal epithelium (recently reviewed here [ 24 , 25 , 26 ]). Additionally, we highlight the role of lipid metabolism in cell communication and crosstalk within the tumor microenvironment.…”