Sorting nexin 10 sustains PDGF receptor signaling in glioblastoma stem cells via endosomal protein sorting

Abstract

Glioblastoma is the most malignant primary brain tumor for which the prognosis remains dismal even with aggressive surgical, medical, and radiation therapies. Glioblastoma stem cells (GSCs) promote therapeutic resistance and cellular heterogeneity due to their self-renewal properties and capacity for plasticity. To understand the molecular processes essential for maintaining GSCs, we performed an integrative analysis comparing active enhancer landscapes, transcriptional profiles, and functional genomics profiles of GSCs and non-neoplastic neural stem cells (NSCs). We identified sorting nexin 10 (SNX10), an endosomal protein sorting factor, as selectively expressed in GSCs compared to NSCs and essential for GSC survival. Targeting SNX10 impaired GSC viability and proliferation, induced apoptosis, and reduced self-renewal capacity. Mechanistically, GSCs utilized endosomal protein sorting to promote platelet-derived growth factor receptor β (PDGFRβ) proliferative and stem cell signaling pathways through post-transcriptional regulation of the PDGFR tyrosine kinase. Targeting SNX10 expression extended survival of orthotopic xenograft-bearing mice, and high SNX10 expression correlated with poor glioblastoma patient prognosis, suggesting its potential clinical importance. Thus, our study reveals an essential connection between endosomal protein sorting and oncogenic receptor tyrosine kinase signaling and suggests that targeting endosomal sorting may represent a promising therapeutic approach for glioblastoma treatment.

Ropivacaine inhibits the proliferation and metastasis of gastric cancer cells via the SNX10/SRC/STAT3 pathway

“…Accumulating studies have shown the association of SNX10 and multiple cancers, such as colorectal cancer (Le et al., 2018; Zhang, Yang, et al., 2020) and glioblastoma (Gimple et al., 2023). However, it is not clear whether SNX10 has been implicated in gastric cancer as well.…”

“…Therefore, AGS cells treated with 4.0 mM Rop were used in the subsequent experiments. SNX10 deficiency has been reported to be associated with proliferation of colorectal cancer (Le et al., 2018; Zhang, Yang, et al., 2020) and glioblastoma (Gimple et al., 2023). Whether SNX10 is involved in the Rop‐induced inhibitory effect on the proliferation of gastric cancer cells remains unclear.…”

“…Sorting nexin 10 (SNX10) is a protein that plays a critical role in intracellular protein trafficking and sorting (Cullen, 2008; Cullen & Korswagen, 2011). SNX10 has been demonstrated to be associated with cervical squamous cell carcinoma (Jiang et al., 2021), colorectal cancer (Le et al., 2018; Zhang, Yang, et al., 2020), and glioblastoma (Gimple et al., 2023). The non‐receptor tyrosine kinase SRC regulates multiple cellular processes, including cell growth, migration, and invasion (Baumgartner et al., 2008; Yang et al., 2014).…”

“…been demonstrated to be associated with cervical squamous cell carcinoma (Jiang et al, 2021), colorectal cancer (Le et al, 2018;, and glioblastoma (Gimple et al, 2023). The non-receptor tyrosine kinase SRC regulates multiple cellular processes, including cell growth, migration, and invasion (Baumgartner et al, 2008;Yang et al, 2014).…”

Bayesian shrinkage models for integration and analysis of multiplatform high‐dimensional genomics data

“…IL8 [11] Mixed effect: SNX10 [14,23] MARS, CHI3L1 [45,43] RANBP17 [45] M-effect: JMJD1A, OLIG2 [3] CBR1 [22] FPRL1 [26] SYTL2 [9] P2RY6, CCR1 [34] TLR2 [36] F3 [13] SECTM1 [35] GPRC5A [48] PIP4K2C [1] APOC2 [27] TKTL1 [16] ZNF135, PCYOX1 [8] LSP1, ZCCHC2, HPGD [31] Note: Those without citations are new genes needed to be further studied. of RANBP17, CHI3L1, and SNX10 are with prognosis of GBM and their methylation status are suggested to play an important role in GBM or other cancer.…”