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.

Keywords: colorectal cancer; metabolic reprogramming; metabolism; protein kinase; signaling pathways.

FIGURE 1

Regulation of the Warburg effect via oncogenic signaling in CRC. The red sign indicates inhibition, while the green arrow indicates promotion.

FIGURE 2

Regulation of amino acids and lipid metabolism via oncogenic signaling in CRC cells. The red sign indicates inhibition, while the green arrow indicates promotion.

FIGURE 3

Metabolic reprogramming through oncogenic signaling during CRC initiation and progression as well as metabolic reprogramming in CRC stem cells. The red sign indicates inhibition while the green arrow indicates promotion.