Potential role of mitochondria in gastric cancer detection: Fission and glycolysis

Abstract

Gastric cancer (GC) is characterized by high morbidity and mortality rates worldwide. Helicobacter pylori infection, high salt intake, smoking, alcohol, low fiber intake, family history of GC, obesity and precancerous lesions, including chronic atrophic gastritis and intestinal metaplasia, are considered general risk factors for GC. Image enhancement endoscopy methods, which improve the visualization of mucosal structures and vascularity, may be used for the early diagnosis of GC, such as narrow band imaging, which can reveal fine details of subtle superficial abnormalities of early gastric cancer (EGC). Mitochondria are well-known for their role in producing ATP via the tricarboxylic acid cycle. In cancer cells, the energetic metabolism can be reprogrammed as anaerobic glycolysis for energy production and anabolic growth. In addition to their dominant metabolic functions, mitochondria participate in several central signaling pathways, such as the apoptotic pathway and NLRP3 inflammasome activation. Conversely, mitochondrial dynamics, including fission/fusion and mitophagy, can also contribute to the pathogenesis of cancer. The dysfunction and dysregulation of mitochondria have been associated with several ageing and degenerative diseases, as well as cancer. The present review focuses on energy metabolism and mitochondrial dynamics, and summarizes the changes in gastric carcinogenesis, the diagnosis of EGC and indicates potential targeted treatments.

Keywords: diagnosis of early gastric cancer; mitochondrial dynamics; reprogrammed energy metabolism.

Figure 1.

Different mitochondrial dynamics and energy metabolism in an epithelial cell subjected to chronic inflammation. Chronic inflammation causes the injury of epithelial cells. Mitochondria is involved in further innate immune responses, including cGAS-STING signaling, TLR-9 and NLRP3 inflammasome formation following the release of mtDNA. Mitochondria is also associated with apoptosis. When atrophic epithelial cells preserve their programed cell death ability and surrounding inflammation is sufficiently severe, cells undergo apoptosis instead of necrosis. Chronic inflammation can also damage mitochondria and lead to changes in mitochondrial metabolism and dynamics via HIF-1, AMPK and MOMP. Fission and glycolysis promote cell proliferation and invasion. Fusion and OXPHOS are compatible with cell survival. Mitophagy protects both normal and cancer cells by selectively eliminating damaged mitochondria. Green outline represents proliferation, blue outline represents survival and the text without boxes represent apoptosis. cGAS, cyclic GMP–AMP synthase; STING, stimulator of interferon genes; TLR-9, Toll-like receptor-9; NLRP3, NOD-like receptor family pyrin domain-containing 3; mtDNA, mitochondrial DNA; HIF-1, hypoxia-inducible factor-1; AMPK, AMP-activated protein kinase; MOMP, mitochondrial outer membrane permeabilization; OXPHOS, oxidative phosphorylation; ETC, electron transport chain; mtROS, mitochondrial ROS; ΔP, increased potential; cytoC, cytochrome c; PGC1, proliferator-activated receptor-γ coactivator.