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. Shields, 2004). The treatment of RB is multimodal. Basic treatment methods are chemotherapy, radiation therapy, enucleation, and focal treatment including transpupillary thermotherapy, cryotherapy, and laser photocoagulation, all playing a vital role (Yanik et al., 2015). Recently, chemotherapy has become the most

β-Asarone Attenuates Aβ-Induced Neuronal Damage in PC12 Cells Overexpressing APPswe by Restoring Autophagic Flux

“…When APPswe-overexpressing cells were co-cultured with CQ, the expression levels of p62 increased, suggesting an increase in the number of autophagosomes and inhibition of autophagic flux (Lin et al, 2019). Additionally, the expression levels of Beclin-1, LC3-Ⅱ, and Aβ 1-42 did not change, and the accumulation of autophagosomes or alkalized autolysosomes was also increased, confirming this effect (Sun et al, 2020). When APPswe-overexpressing cells were co-cultured with CQ and β-asarone, there was no significant difference in the expression of Beclin-1, p62, LC3-Ⅱ, and Aβ 1-42 .…”

Crosstalk between Lipid Rafts and Aging: New Frontiers for Delaying Aging

“…LRs appear to be essential for regulating the mTOR pathway by promoting phosphoinositide 3-kinase (PI3K) recruitment and V-akt murine thymoma viral oncogene homolog (Akt) activation [ 61 , 62 ]. Moreover, phosphatase and tensin homologue protein (PTEN) can suppress the PTEN/Akt/mTORC1 pathway, thereby activating autophagy by mobilizing the LR domain [ 63 , 64 ]. As an integral component of LRs, cholesterol is another factor that affects autophagy.…”

Recent Advances in Understanding the Role of Autophagy in Paediatric Brain Tumours

“…XIST silencing suppresses autophagy, tumour proliferation, and enhances apoptosis, additionally sensitizing RB cells to vincristine [ 138 ], the efficacy of which is often limited because of chemoresistance. In this respect, it has recently been discovered that CD24, a plasma membrane GPI-anchored protein being overexpressed in RB and representing a poor prognostic factor in several tumours including RB [ 139 ], impairs RB sensitivity to vincristine by means of promoting autophagy activation [ 140 ]. Particularly, CD24 is responsible for the recruitment of phosphatase and tensin homolog (PTEN) to lipid rafts, which is then able to convert phosphatidylinositol 3,4,5-trisphosphate (PIP3) to PI(4,5)P2, thus inhibiting the activation of PI3K/AKT/mTOR pathway and promoting autophagy.…”