CD24 blunts the sensitivity of retinoblastoma to vincristine by modulating autophagy.

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.

• Authors: Jie Sun, Dongju Feng, Huiyu Xi, Jiajing Luo, Zewei Zhou, Qinghuai Liu, Yun Chen, Qing Shao
• Journal: Molecular oncology (Mol Oncol) Vol. 14 Issue 8 Pg. 1740-1759 (08 2020) ISSN: 1878-0261 [Electronic] United States
• PMID: 32394616 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

Chemical References

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

Topics

• Animals
• Autophagosomes (drug effects, metabolism, ultrastructure)
• Autophagy (drug effects, 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, metabolism)
• Mice, Inbred BALB C
• Mice, Nude
• PTEN Phosphohydrolase (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Retinoblastoma (drug therapy, genetics, metabolism, pathology)
• Signal Transduction (drug effects)
• Vincristine (pharmacology, therapeutic use)