Glycolytic enzymes in non-glycolytic web: functional analysis of the key players

Area of Science:

• Oncology
• Metabolic pathways
• Cancer biology

Background:

• Cancer cells exhibit metabolic reprogramming, notably increased glycolysis and decreased oxidative phosphorylation (OXPHOS), to survive the tumor microenvironment.
• Glycolysis supports ATP synthesis, NADH regeneration, and biosynthesis, enabling cancer cell proliferation under nutrient-limited and hypoxic conditions.
• Glycolytic enzymes are implicated in oncogenic activation and represent promising targets for anti-cancer therapies.

Purpose of the Study:

• To review the non-canonical functions of glycolytic enzymes and their intermediates.
• To elucidate the mechanisms underlying these non-glycolytic activities in the tumor microenvironment.
• To highlight the role of these enzymes in cancer cell survival and proliferation.

Main Methods:

• Literature review of current findings on glycolytic enzyme functions.
• Analysis of mechanisms related to non-glycolytic actions of glycolytic enzymes.
• Synthesis of information on the role of these enzymes in maintaining the tumor microenvironment.

Main Results:

• Glycolytic enzymes possess non-canonical functions beyond energy production.
• These functions include roles in transcriptional regulation, autophagy, epigenetics, inflammation, signaling, redox balance, and metabolism.
• Intermediates of glycolysis also contribute to these diverse cellular processes.

Conclusions:

• Glycolytic enzymes and their intermediates play multifaceted roles in the tumor microenvironment.
• Understanding these non-canonical functions is crucial for developing novel anti-cancer strategies.
• Targeting these enzymes may offer new therapeutic avenues beyond their metabolic roles.