ARP2/3 Regulates Fatty Acid Synthesis by Modulating Lipid Droplets' Motility

Int J Mol Sci. 2022 Aug 5;23(15):8730. doi: 10.3390/ijms23158730.

Abstract

The breakdown of lipid droplets (LDs) provides energy and contributes to the proliferation and migration of cancer cells. Recent studies have suggested that motility plays a key role in LD breakdown. However, the molecular mechanisms underlying LD motility were poorly characterized. In this study, we examined the function of microfilament-associated proteins 2 and 3 (ARP2 and ARP3) in regulating LDs’ motility in Hela cells. ARP2/3 mediated the LDs’ physical contact with F-actin and promoted the recruitment of Myosin Heavy Chain 9 (MYH9). MYH9 regulated the LD content by binding with LDs and ARP2/3. The number of LDs and TG content was increased after MYH9 interfered. The genes related to FA-related genes and neutral lipid synthesis-related genes were significantly increased (p < 0.05) when ARP2 and ARP3 were overexpressed. Bioinformatic analysis indicated that the high expression of ARP2/3 was associated with a poorer prognosis in cervical squamous cell carcinoma (CSCC). This study showed the effect of cytoskeletal filaments on LD metabolism in cancer cells.

Keywords: ARP2; ARP3; Hela; MYH9; lipid droplets; motility.

MeSH terms

  • Actin-Related Protein 2-3 Complex / metabolism*
  • Actins* / metabolism
  • Cytoskeletal Proteins / metabolism
  • Fatty Acids / metabolism
  • HeLa Cells
  • Humans
  • Lipid Droplets* / metabolism
  • Lipid Metabolism
  • Microfilament Proteins / metabolism

Substances

  • Actin-Related Protein 2-3 Complex
  • Actins
  • Cytoskeletal Proteins
  • Fatty Acids
  • Microfilament Proteins