CPT1C-mediated fatty acid oxidation facilitates colorectal cancer cell proliferation and metastasis

Acta Biochim Biophys Sin (Shanghai). 2023 Apr 20;55(8):1301-1309. doi: 10.3724/abbs.2023041.

Abstract

Fatty acid oxidation (FAO) has been proven to be an accomplice in tumor progression. Carnitine palmitoyltransferase 1C (CPT1C), a rate-limiting enzyme in FAO, mainly functions to catalyze fatty acid carnitinylation and guarantee subsequent entry into the mitochondria for FAO in colorectal cancer (CRC). Gene expression data and clinical information extracted from The Cancer Genome Atlas (TCGA) database show significantly higher expression of CPT1C in patients with metastatic CRC ( P=0.005). Moreover, overexpression of CPT1C is correlated with worse relapse-free survival in CRC (HR 2.1, P=0.0006), while no statistical significance is indicated for CPT1A and CPT1B. Further experiments demonstrate that downregulation of CPT1C expression leads to a decrease in the FAO rate, suppression of cell proliferation, cell cycle arrest and repression of cell migration in CRC, whereas opposite results are obtained when CPT1C is overexpressed. Furthermore, an FAO inhibitor almost completely reverses the enhanced cell proliferation and migration induced by CPT1C overexpression. In addition, analysis of TCGA data illustrates a positive association between CPT1C expression and HIF1α level, suggesting that CPT1C is a transcriptional target of HIF1α. In conclusion, CPT1C overexpression indicates poor relapse-free survival of patients with CRC, and CPT1C is transcriptionally activated by HIF1α, thereby promoting the proliferation and migration of CRC cells.

Keywords: CPT1C; cell migration; cell proliferation; colorectal cancer; fatty acid oxidation.

MeSH terms

  • Carnitine O-Palmitoyltransferase* / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Colorectal Neoplasms* / genetics
  • Fatty Acids* / metabolism
  • Humans
  • Neoplasm Recurrence, Local*

Substances

  • Fatty Acids
  • CPT1B protein, human
  • Carnitine O-Palmitoyltransferase

Grants and funding

This work was supported by the grants from the National Natural Science Foundation of China (No. 81802374), the Shanghai Municipal Health Commission (No. 20194Y0398) and the Shanghai Municipal Key Clinical Specialty (No. shslczdzk06802).