Energy Metabolic Plasticity of Colorectal Cancer Cells as a Determinant of Tumor Growth and Metastasis

Abstract

Metabolic plasticity is the ability of the cell to adjust its metabolism to changes in environmental conditions. Increased metabolic plasticity is a defining characteristic of cancer cells, which gives them the advantage of survival and a higher proliferative capacity. Here we review some functional features of metabolic plasticity of colorectal cancer cells (CRC). Metabolic plasticity is characterized by changes in adenine nucleotide transport across the outer mitochondrial membrane. Voltage-dependent anion channel (VDAC) is the main protein involved in the transport of adenine nucleotides, and its regulation is impaired in CRC cells. Apparent affinity for ADP is a functional parameter that characterizes VDAC permeability and provides an integrated assessment of cell metabolic state. VDAC permeability can be adjusted via its interactions with other proteins, such as hexokinase and tubulin. Also, the redox conditions inside a cancer cell may alter VDAC function, resulting in enhanced metabolic plasticity. In addition, a cancer cell shows reprogrammed energy transfer circuits such as adenylate kinase (AK) and creatine kinase (CK) pathway. Knowledge of the mechanism of metabolic plasticity will improve our understanding of colorectal carcinogenesis.

Keywords: VDAC; adenylate kinase; aerobic glycolysis; creatine kinase; mitochondria; oxidative phosphorylation; tumor energy metabolism.