Targeting GPX2 to disrupt lipid homeostasis and enhance cisplatin sensitivity in diffuse gastric cancer
Yanmei Zhu, Yichun Ma, Wenying Li, Yani Pan, Yue Wang, Qiange Ye, Yinya Pan, Ying Xiang, Ping Jiang, Yi Fang, Lei Xu, Na Liu, Gaifang Liu, Zhangding Wang, Guifang Xu
TL;DR
This study shows that targeting GPX2 can improve cisplatin effectiveness in treating diffuse gastric cancer by disrupting lipid metabolism and increasing cancer cell death.
Contribution
The study identifies GPX2 as a novel therapeutic target and prognostic biomarker for diffuse gastric cancer.
Findings
GPX2 is significantly upregulated in diffuse gastric cancer tissues and serves as an independent prognostic indicator.
GPX2 suppression disrupts lipid homeostasis and increases acylcarnitine levels, impairing mitochondrial function and inducing apoptosis.
Inhibiting GPX2 enhances cisplatin sensitivity in gastric cancer cells by promoting apoptosis.
Abstract
Diffuse gastric cancer (DGC) is characterized by high malignancy and metastasis rate, and poorly understood etiology, culminating in dismal patient outcomes. Here, through comprehensive analysis, we identified that glutathione peroxidase 2 (GPX2) plays a pivotal role in the progression of DGC by regulating lipid metabolism. This study demonstrates that GPX2 is markedly upregulated in DGC tissues, establishing its potential as an independent prognostic indicator. Functionally, GPX2 suppression disrupts lipid droplet formation and lipid homeostasis, leading to increased acylcarnitine levels that impair mitochondrial function. This disruption synergizes with endoplasmic reticulum stress to trigger apoptosis in gastric cancer cells. Notably, inhibiting GPX2 enhances the efficacy of cisplatin by sensitizing cancer cells to apoptosis. These insights identify GPX2 not only as a vital…
Genes, proteins, chemicals, diseases, species, mutations and cell lines named across the full text — each resolved to its canonical identifier and authoritative record.
Click any figure to enlarge with its caption.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8Peer Reviews
No public reviews on file for this paper yet. If you reviewed it on a platform where reviews are public (OpenReview, ICLR, NeurIPS, ICML), you can paste yours below so the community can read it here.
Videos
No videos yet. Explain this paper in a talk, walkthrough, or lecture? Add one.
Taxonomy
TopicsCancer, Lipids, and Metabolism · Steroid Chemistry and Biochemistry · Glutathione Transferases and Polymorphisms