Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Glioblastoma (GBM) is the most malignant primary brain tumor in adults. Temozolomide (TMZ) stands for the first-line chemotherapeutic agent against GBM. TMZ resistance is an important factor contributing to the poor prognosis of GBM, but the underlying molecular mechanisms are unclear. Previous studies have suggested that KIF4A may be an indicator of poor prognosis in glioma patients, but the association of KIF4A with TMZ resistance has never been investigated. The detection of ferroptosis levels in GBM cells was accomplished through the utilization of ROS, MDA, JC-1, and Western blot analysis. The assessment of TMZ resistance was performed through the implementation of CCK8, cell cloning, and cell cycle analysis. The identification of downstream targets of KIF4A was facilitated by protein profiling and immunofluorescence. KIF4A inhibits ferroptosis in GBM cells through the CHMP4B/GPX4 axis and promotes TMZ resistance. Knockdown of KIF4A or CHMP4B sensitized GBM cells to chemotherapy. In addition, KIF4A induced epithelial-mesenchymal transition in GBM cells, which synergistically promoted TMZ resistance.The present study elucidates a novel mechanism of TMZ resistance in glioblastoma through the CHMP4B/GPX4 axis. Based on these findings, targeting KIF4A may offer a potential new strategy against GBM.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/mc.70006 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Demethoxycurcumin induces apoptosis and reduces cell migration by affecting AKT/mTOR-dependent autophagy in human glioma U87MG and T98G cell lines.
Mol Biol Rep
September 2025
Dr. B. R. Ambedkar Centre for Biomedical Research North Campus , University of Delhi, 110007, Delhi, India.
Background: Standard treatment for glioblastoma includes chemotherapy, alkylating agents such as temozolomide (TMZ); however, MGMT resistance leads to recurrence. Demethoxycurcumin (DMC) has been reported to inhibit cancer cell growth, induce apoptosis, and prevent metastasis in different cancer models. We investigated the DMC-induced apoptosis and autophagy via inhibition of the AKT/mTOR pathway in human glioma U87MG and T98G cell lines.
View Article and Find Full Text PDFDual-action nanotherapy: Temozolomide-loaded, anti-PD-L1 scFv-functionalized lipid nanocarriers for targeted glioblastoma therapy.
Eur J Pharm Sci
September 2025
Department of Neurology, Massachusetts General Hospital, Boston, MA, 02129, USA; Neuroscience Program, Harvard Medical School, Boston, MA, 02129, USA. Electronic address:
Glioblastoma (GBM) is a highly malignant brain tumor with limited treatment options and poor prognosis. GBM exhibits resistance to conventional therapies, including temozolomide (TMZ), radiotherapy, and immunotherapy, partly due to immunosuppressive mechanisms such as programmed death-ligand 1 (PD-L1) overexpression. To address these challenges, we developed TMZ-loaded nanostructured lipid carriers (NLCs) conjugated with anti-PD-L1 single-chain variable fragments (scFv) for dual chemo-immunotherapy.
View Article and Find Full Text PDFNovel Thioredoxin reductase 1 inhibitor BS1801 relieves treatment resistance and triggers endoplasmic reticulum stress by elevating reactive oxygen species in glioma.
Redox Biol
August 2025
Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, No.119 South 4th Ring Road West, Beijing, China; Chinese Glioma Genome Atlas Network (CGGA) and Asian Glioma Genome Atlas Network (AGGA), Beijing, China; Beijing Engineering Research Center of Target
Glioma patients will inevitably develop resistance to temozolomide (TMZ) leading to tumor recurrence. By comparing genomic differences between primary and recurrent glioma patients, Thioredoxin reductase 1 (TrxR1) was identified as a crucial role in TMZ resistance. Glioma cells elevate the expression level of TXNRD1 to against TMZ-induced reactive oxygen species (ROS), thereby conferring TMZ resistance.
View Article and Find Full Text PDFTemozolomide-Derived Therapeutic Strategies to Overcome Resistance in Glioblastoma.
J Med Chem
September 2025
Department of Chemistry and Biochemistry, The University of Texas at El Paso, El Paso, Texas 79968, United States.
Glioblastoma multiforme (GBM) accounts for nearly half of malignant CNS tumors and has a dismal 5-year survival rate of 5.5%. The current standard of care comprises maximal surgical resection, followed by radiotherapy with concurrent temozolomide (TMZ) and subsequent adjuvant TMZ chemotherapy.
View Article and Find Full Text PDFOvercoming standard-of-care resistance in glioblastoma using nanoparticle-based drug delivery targeting the autophagy pathway.
Biochem Pharmacol
September 2025
Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA. Electronic address:
Glioblastoma (GBM) is the most aggressive and lethal primary brain tumor in adults, characterized by rapid growth, diffuse infiltration, and a dismal prognosis. Despite aggressive treatment involving maximal surgical resection followed by radiotherapy and temozolomide (TMZ) chemotherapy, therapeutic outcomes remain poor due to intrinsic and acquired resistance. Autophagy, a catabolic process that degrades damaged cellular components, plays a critical role in this resistance by enabling tumor cells to survive under metabolic, hypoxic, and therapeutic stress conditions.
View Article and Find Full Text PDF