CD24 blunts the sensitivity of retinoblastoma to vincristine by modulating autophagy

Mol Oncol. 2020 Aug;14(8):1740-1759. doi: 10.1002/1878-0261.12708. Epub 2020 Jun 13.

Abstract

Retinoblastoma (RB) is the most common childhood malignant intraocular tumor. The clinical efficacy of vincristine (VCR) in the treatment of RB is severely limited by drug resistance. Here, we found that CD24, a GPI-anchored protein, was overexpressed in human RB tissues and RB cell lines, and was associated with the sensitivity of RB cells in response to VCR therapy. We demonstrated that CD24 plays a critical role in impairing RB sensitivity to VCR via regulating autophagy. Mechanistically, CD24 recruits PTEN to the lipid raft domain and regulates the PTEN/AKT/mTORC1 pathway to activate autophagy. Lipid raft localization was essential for CD24 recruitment function. Collectively, our findings revealed a novel role of CD24 in regulating RB sensitivity to VCR and showed that CD24 is a potential target for improving chemotherapeutic sensitivity and RB patient outcomes.

Keywords: CD24; autophagy; lipid raft; retinoblastoma; vincristine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagosomes / drug effects
  • Autophagosomes / metabolism
  • Autophagosomes / ultrastructure
  • Autophagy* / drug effects
  • Autophagy* / genetics
  • CD24 Antigen / metabolism*
  • Cell Line, Tumor
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glycosylphosphatidylinositols / metabolism
  • Humans
  • Male
  • Mechanistic Target of Rapamycin Complex 1 / metabolism
  • Membrane Microdomains / drug effects
  • Membrane Microdomains / metabolism
  • Mice, Inbred BALB C
  • Mice, Nude
  • PTEN Phosphohydrolase / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Retinoblastoma / drug therapy
  • Retinoblastoma / genetics
  • Retinoblastoma / metabolism*
  • Retinoblastoma / pathology*
  • Signal Transduction / drug effects
  • Vincristine / pharmacology
  • Vincristine / therapeutic use*

Substances

  • CD24 Antigen
  • Glycosylphosphatidylinositols
  • Vincristine
  • Mechanistic Target of Rapamycin Complex 1
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase