Colorectal polyps increase the glycolytic activity.

Area of Science:

• Biochemistry
• Cancer Metabolism
• Molecular Biology

Background:

• Colorectal cancer (CRC) energy metabolism is not fully understood, with research suggesting a reliance on mitochondrial respiration rather than pure glycolysis.
• The metabolic changes during the transition from normal tissue to polyps and then to CRC are largely unexplored.
• Identifying metabolic adaptations during tumorigenesis could lead to early diagnostic biomarkers and novel therapeutic strategies.

Purpose of the Study:

• To investigate and describe the metabolic reprogramming occurring during colorectal cancer (CRC) development, from precancerous polyps to tumors.
• To compare the bioenergetic phenotype of polyps, CRC tissues, and normal tissues.
• To identify molecular and functional changes associated with metabolic adaptations in CRC development.

Main Methods:

• High-resolution respirometry was used to assess cellular respiration and mitochondrial function.
• Quantitative reverse transcription PCR (qRT-PCR) was employed to measure gene expression levels.
• Human colorectal cancer and polyp tissue samples were analyzed.

Main Results:

• Colon polyps exhibited a more glycolytic bioenergetic phenotype compared to both CRC tumors and normal tissues.
• Increased expression of key glycolytic genes (GLUT1, HK, LDHA, MCT) was observed in polyps.
• Despite enhanced glycolysis, polyp cells maintained a highly functional oxidative phosphorylation (OXPHOS) system.
• Intracellular energy transfer pathways were rearranged in polyps, with increased expression of adenylate kinase (AK) and creatine kinase (CK) isoforms.
• CRC development was associated with decreased glycolysis, maintained OXPHOS, and downregulation of CK and specific AK isoforms (AK1, AK2).

Conclusions:

• Colorectal polyps display a distinct metabolic profile characterized by increased glycolysis coupled with functional OXPHOS.
• Metabolic reprogramming during polyp formation involves alterations in intracellular energy transfer systems.
• The shift towards decreased glycolysis and altered energy transfer pathways appears crucial for CRC progression.