To be or not to be a fat burner, that is the question for cpt1c in cancer cells

Cell Death Dis. 2023 Jan 24;14(1):57. doi: 10.1038/s41419-023-05599-1.

Abstract

There is an urgent need to identify reliable genetic biomarkers for accurate diagnosis, prognosis, and treatment of different tumor types. Described as a prognostic marker for many tumors is the neuronal protein carnitine palmitoyltransferase 1 C (CPT1C). Several studies report that CPT1C is involved in cancer cell adaptation to nutrient depletion and hypoxia. However, the molecular role played by CPT1C in cancer cells is controversial. Most published studies assume that, like canonical CPT1 isoforms, CPT1C is a mediator of fatty acid transport to mitochondria for beta-oxidation, despite the fact that CPT1C has inefficient catalytic activity and is located in the endoplasmic reticulum. In this review, we collate existing evidence on CPT1C in neurons, showing that CPT1C is a sensor of nutrients that interacts with and regulates other proteins involved in lipid metabolism and transport, lysosome motility, and the secretory pathway. We argue, therefore, that CPT1C expression in cancer cells is not a direct regulator of fat burn, but rather is a regulator of lipid metabolic reprograming and cell adaptation to environmental stressors. We also review the clinical relevance of CPT1C as a prognostic indicator and its contribution to tumor growth, cancer invasiveness, and cell senescence. This new and integrated vision of CPT1C function can help better understand the metabolic plasticity of cancer cells and improve the design of therapeutic strategies.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carnitine O-Palmitoyltransferase* / genetics
  • Carnitine O-Palmitoyltransferase* / metabolism
  • Humans
  • Hypoxia / metabolism
  • Neoplasms* / genetics
  • Neoplasms* / metabolism
  • Neoplasms* / physiopathology
  • Neurons / metabolism
  • Oxidation-Reduction

Substances

  • Carnitine O-Palmitoyltransferase
  • CPT1B protein, human