SLMO2 Promotes Chemoresistance in Glioblastoma by Regulating BNIP3-Dependent Mitophagy via the NF-κB/HIF-1α Axis.

Authors

Ning Yang, Yuan Qiao, Jing Wu, Chao Niu, Jianpeng Wang, Shiming Sun, Chunyan Liu, Jingtao Chen, Shan Zhu

Published in

Pharmacological research. Pages 109688. Oct 14, 2026. Epub Oct 14, 2026.

Abstract

Glioblastoma (GBM) is a highly aggressive malignancy, with chemoresistance acting as a major hurdle that severely limits clinical efficacy and long-term prognosis. Mitophagy, a core mechanism of mitochondrial quality control, enables tumor cells to adapt to chemotherapy-induced stress and maintain survival. However, its regulatory mechanism in GBM chemoresistance remains poorly understood. Here, we identify SLMO2 as a key factor mediating chemoresistance in GBM. Low-dose TMZ induces protective mitophagy, whereas SLMO2 knockdown abrogates this autophagic defense, thereby sensitizing GBM cells to TMZ-induced apoptosis. Mechanistically, TMZ treatment upregulates SLMO2, which potently activates HIF-1α signaling to transcriptionally drive BNIP3-mediated mitophagy, a process dependent on ROS-NF-κB signaling. Notably, this SLMO2-mediated cascade is also engaged under cisplatin-induced stress, indicating a broader role in chemoresistance. Collectively, our findings reveal that SLMO2 promotes chemoresistance in GBM by regulating BNIP3-mediated mitophagy. Targeting SLMO2 disrupts mitochondrial homeostasis by this process, offering a novel therapeutic strategy for enhancing chemosensitivity in GBM.

PMID:
42874824
Bibliographic data and abstract were imported from PubMed on 15 Oct 2026.

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