SLC27A2 mediates FAO in colorectal cancer through nongenic crosstalk regulation of the PPARs pathway

• Published in: BMC cancer Vol. 23; no. 1; p. 335
• Main Authors: Shang, Kun, Ma, Nina, Che, Juanjuan, Li, Huihui, Hu, Jiexuan, Sun, Haolin, Cao, Bangwei
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 11.04.2023; BioMed Central; BMC
• Subjects: Analysis; Antibodies; Cancer; Care and treatment; Cell cycle; Coenzyme A Ligases - metabolism; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms; Correlation analysis; Development and progression; Diagnosis; Experiments; FAO; Fatty acids; Fatty Acids - metabolism; Genes; Glycogen Synthase Kinase 3 beta; Health aspects; Homeostasis; Humans; Immunofluorescence; Ligands; Lipid metabolism; Lipids; Membrane proteins; Metabolism; Metabolites; Metastasis; Mitochondria; Nuclear receptors; Peroxisomal membrane protein; Peroxisome Proliferator-Activated Receptors; Peroxisomes; Physiological aspects; PPARs; Protein-protein interactions; Proteins; Receptors, Cytoplasmic and Nuclear; SLC27A2; Statistical analysis; Tumorigenesis; Western blotting; China; United States > US; Japan; FAO; SLC27A2; PPARs; Colorectal cancer
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-023-10816-3

Peroxisome proliferator activated receptors (PPARs) are a nuclear hormone receptors superfamily that is closely related to fatty acid (FA) metabolism and tumor progression. Solute carrier family 27 member 2 (SLC27A2) is important for FA transportation and metabolism and is related to cancer progression. This study aims to explore the mechanisms of how PPARs and SLC27A2 regulate FA metabolism in colorectal cancer (CRC) and find new strategies for CRC treatment. Biological information analysis was applied to detect the expression and the correlation of PPARs and SLC27A2 in CRC. The protein-protein interaction (PPI) interaction networks were explored by using the STRING database. Uptake experiments and immunofluorescence staining were used to analyse the function and number of peroxisomes and colocalization of FA with peroxisomes, respectively. Western blotting and qRT‒PCR were performed to explore the mechanisms. SLC27A2 was overexpressed in CRC. PPARs had different expression levels, and PPARG was significantly highly expressed in CRC. SLC27A2 was correlated with PPARs in CRC. Both SLC27A2 and PPARs were closely related to fatty acid oxidation (FAO)‒related genes. SLC27A2 affected the activity of ATP Binding Cassette Subfamily D Member 3 (ABCD3), also named PMP70, the most abundant peroxisomal membrane protein. We found that the ratios of p-Erk/Erk and p-GSK3β/GSK3β were elevated through nongenic crosstalk regulation of the PPARs pathway. SLC27A2 mediates FA uptake and beta-oxidation through nongenic crosstalk regulation of the PPARs pathway in CRC. Targeting SLC27A2/FATP2 or PPARs may provide new insights for antitumour strategies.