Role of Endocytosis Proteins in Gefitinib-Mediated EGFR Internalisation in Glioma Cells

Silva, Elisabete Cruz Da; Choulier, Laurence; Thevenard-Devy, Jessica; Schneider, Christophe; Carl, Philippe; Rondé, Philippe; Dedieu, Stéphane; Lehmann, Maxime

doi:10.3390/cells10113258

Cited by 5 publications

(5 citation statements)

References 63 publications

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“…Dysregulated endocytosis and membrane trafficking of RTKs mediated by endosomes maintains glioblastoma malignancy ( 46 ). SNX family proteins have been implicated in endosomal sorting and endosomal homeostatic maintenance.…”

Section: Discussionmentioning

confidence: 99%

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

Gimple¹,

Zhang²,

Wang³

et al. 2023

JCI Insight

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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.

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Section: Discussionmentioning

confidence: 99%

“…endosomes maintains glioblastoma malignancy (46). SNX family proteins have been implicated in endosomal sorting and endosomal homeostasis maintenance.…”

Section: Dysregulated Endocytosis and Membrane Trafficking Of Recepto...mentioning

confidence: 99%

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

Gimple¹,

Zhang²,

Wang³

et al. 2023

JCI Insight

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show abstract

“…A number of patients can benefit from TKI treatment, while others will still suffer from recurrence ( 34 ). It has been reported that internalization of EGFR mediated by endocytosis is one of the direct reasons for TKI treatment failure ( 35 ). In addition, tumors can also become drug resistant through a bypass activation mechanism, leading to poor prognosis ( 36 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of a novel endocytosis‑associated gene signature for prognostic prediction in lung adenocarcinoma

Zhang,

Liang,

Zhang

et al. 2023

Oncol Lett

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Lung cancer is one of the most common malignant solid tumors and the leading cause of cancer-associated mortality worldwide. Endocytosis is an essential physiological activity for cells to maintain membrane homeostasis, and has been reported to serve an important role in tumorigenesis and progression. In the present study, the aim was to construct a prognostic prediction model of endocytosis-associated genes for patients with lung adenocarcinoma (LUAD). The endocytosis-associated gene signature was established using Lasso Cox regression analysis using the training set of the LUAD cohort from The Cancer Genome Atlas (TCGA) database, and verified using two datasets from the Gene Expression Omnibus (GEO) database. Kaplan-Meier survival curves were used to evaluate the effectiveness of the prognostic evaluation of patients with LUAD. Differentially expressed genes were screened in the tumor tissue of patients compared with paired paracancerous tissues. A series of candidate genes associated to the prognosis of patients with LUAD was obtained using univariate Cox's regression analysis. Using the Lasso Cox regression analysis, an appropriate risk model with 18 endocytosis-associated genes was established. A high-risk score was positively correlated with a higher tumor stage and pathologic grade. Patients with LUAD and high-risk scores had shorter survival times, increased intratumor heterogeneities and immune cell infiltration into tumor tissues, compared with those patients with LUAD and low-risk scores. The endocytosis inhibitor chloroquine could repress proliferation and increase the apoptosis of lung cancer cells. In summary, a novel endocytosis-associated gene signature was constructed using TCGA and GEO datasets. Patients with LUAD and high-risk scores, as calculated by the signature, had a poor prognosis and short survival time.

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“…Gefitinib (ZD1839; Iressa), a small molecular weight EGFR kinase inhibitor, has been given approval for the treatment of locally advanced and metastatic non-small cell lung cancer, or NSCLC. [47] A humanised monoclonal antibody called cetuximab (C225; Erbitux interacts the both EGFR and EGFRvIII extracellular domains. It has been authorised for the treatment of head and neck squamous cell carcinoma that has spread or recurred after previous chemotherapy.…”

Section: Molecular Markers Associated With Glioma: Mgmtmentioning

confidence: 99%

Precision Medicine at a Nanoscale: Targeted Nanotechnology as a Promising Strategy for Glioblastoma Therapy

Kumbhar¹,

Waghmare²

2023

Int. J. Res. Publ. Rev.

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Glioblastoma is the deadliest cancer worldwide. Due to its location in the brain and resistance to conventional therapies, glioblastoma is a particularly deadly and aggressive type of brain cancer that is challenging to treat. By enabling precise drug and therapeutic agent delivery to the tumour site, avoiding the blood-brain barrier, as well as minimising negative effects, targeted nanotechnology presents a potential therapy method for glioblastoma. A variety of drugs or therapeutic agents can be carried by nanoparticles, enabling a combination of treatments. They can also be utilised in non-invasive cancer treatments like magnetic hyperthermia and photothermal therapy, which use heat to kill cancer cells. Additionally, nanoparticles can be created to target particular tumour markers, enabling personalised treatment for different patients.

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Role of Endocytosis Proteins in Gefitinib-Mediated EGFR Internalisation in Glioma Cells

Cited by 5 publications

References 63 publications

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

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

Identification of a novel endocytosis‑associated gene signature for prognostic prediction in lung adenocarcinoma

Precision Medicine at a Nanoscale: Targeted Nanotechnology as a Promising Strategy for Glioblastoma Therapy

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