PFKP silencing suppresses tumor growth via the AXL-MET axis

Int J Biol Sci. 2024 Nov 11;20(15):6056-6072. doi: 10.7150/ijbs.100525. eCollection 2024.

Abstract

PFKP (Phosphofructokinase, Platelet Type isoform), as an essential metabolic enzyme, contributes to the high glycolysis rates seen in cancers while its role in oncogenic pathways, especially from a non-metabolic aspect, is not fully understood. We found that PFKP was highly expressed in NSCLC and was related to poor patient survival. Knockdown of PFKP significantly inhibited cell proliferation, colony formation, invasion, and migration of NSCLC cells. Nanoparticles-mediated PFKP silencing can inhibit tumor growth in vivo. Mechanistically, we found that PFKP can bind with AXL and promote its phosphorylation at Y779, thus activating the AXL signaling pathway and promoting MET phosphorylation. In addition, several glycolysis, glutaminolysis, and TCA cycle proteins were downregulated following PFKP silencing. PFKP has an oncogenic role in cancer progression in vitro and in vivo. Beyond its known role in glycolysis, PFKP also has a non-metabolic function in affecting lung cancer progression by interacting with the AXL-MET axis, thus indicating a potential therapeutic target for lung cancer.

Keywords: AXL; MET.; PFKP; glycolysis; lung cancer.

MeSH terms

  • Animals
  • Axl Receptor Tyrosine Kinase*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation* / genetics
  • Female
  • Glycolysis
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Phosphorylation
  • Proto-Oncogene Proteins c-met / genetics
  • Proto-Oncogene Proteins c-met / metabolism
  • Proto-Oncogene Proteins* / genetics
  • Proto-Oncogene Proteins* / metabolism
  • Receptor Protein-Tyrosine Kinases* / genetics
  • Receptor Protein-Tyrosine Kinases* / metabolism
  • Signal Transduction

Substances

  • Receptor Protein-Tyrosine Kinases
  • Axl Receptor Tyrosine Kinase
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-met