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.
Highlights
Despite the advancement in early detection and medical treatments in recent decades, cancer incidence and mortality continue to increase gradually, as estimated in Global Cancer Statistic (GLOBOCAN) database under The International Agency for Research of Cancer (IARC) and the World Health Organization (WHO)
Xanthohumol directly suppressed the phosphorylation of Epidermal growth factor receptor (EGFR) and EGFR downstream kinases Akt to downregulate the activity of HKII, resulting in a lower rate of glycolysis and activation of mitochondrial-induced apoptosis in colorectal cancer (CRC) cells (Liu et al, 2019)
signal transducer and activator of transcription 3 (STAT3) and increased the expression of c-MYC and glycolytic enzymes, such as GLUT1 and LDH, resulting in higher glucose uptake and lactate production (Qu et al, 2017). These results suggest that inflammation could induce the reprogramming of glucose metabolism in CRC cells via the STAT3/c-MYC pathway
Summary
Despite the advancement in early detection and medical treatments in recent decades, cancer incidence and mortality continue to increase gradually, as estimated in Global Cancer Statistic (GLOBOCAN) database under The International Agency for Research of Cancer (IARC) and the World Health Organization (WHO). CRC arises from the glandular epithelial cells of the large intestine when specific cells undergo a series of genetic and epigenetic mutations to become hyper-proliferative and cancerous over time (Ewing et al, 2014; Dekker et al, 2019). These cancerous cells form a benign adenoma at an early stage, in which some progress into carcinoma and metastasize to other organs at the later stage of malignancy (Dekker et al, 2019). A deeper understanding of the protein kinases and signaling pathways involved in the metabolic reprogramming in CRC will provide insight into discovering new therapeutic targets
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