Nasopharyngeal carcinoma (NPC) is an epithelia-derived malignancy with a distinctive geographic distribution. Cystathionine γ-lyase (CSE) is involved in cancer development and progression. Nevertheless, the role of CSE in the growth of NPC is unknown. In this study, we found that CSE levels in human NPC cells were higher than those in normal nasopharyngeal cells. CSE overexpression enhanced the proliferative, migrative, and invasive abilities of NPC cells and CSE downregulation exerted reverse effects. Overexpression of CSE decreased the expressions of cytochrome C, cleaved caspase (cas)-3, cleaved cas-9, and cleaved poly-ADP-ribose polymerase, whereas CSE knockdown exhibited reverse effects. CSE overexpression decreased reactive oxygen species (ROS) levels and the expressions of phospho (p)-extracellular signal-regulated protein kinase 1/2, p-c-Jun N-terminal kinase, and p-p38, but promoted the expressions of p-phosphatidylinositol 3-kinase (PI3K), p-AKT, and p-mammalian target of rapamycin (mTOR), whereas CSE knockdown showed oppose effects. In addition, CSE overexpression promoted NPC xenograft tumor growth and CSE knockdown decreased tumor growth by modulating proliferation, angiogenesis, cell cycle, and apoptosis. Furthermore, DL-propargylglycine (an inhibitor of CSE) dose-dependently inhibited NPC cell growth via ROS-mediated mitogen-activated protein kinase (MAPK) and PI3K/AKT/mTOR pathways without significant toxicity. In conclusion, CSE could regulate the growth of NPC cells through ROS-mediated MAPK and PI3K/AKT/mTOR cascades. CSE might be a novel tumor marker for the diagnosis and prognosis of NPC. Novel donors/drugs that inhibit the expression/activity of CSE can be developed in the treatment of NPC.
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The data of the study are available from the corresponding author on reasonable request.
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This work was supported by grants from the National Natural Science Foundation of China (Nos. 81802718, U1504817), the Foundation of Science & Technology Department of Henan Province, China (Nos. 202102310480, 192102310151), the Training Program for Young Backbone Teachers of Institutions of Higher Learning in Henan Province, China (No. 2020GGJS038), and the Science Foundation for Young Talents of Henan University College of Medicine, China (No. 2019013).
The authors declare no competing interests.
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Animal experiments were approved by the Committee of Medical Ethics and Welfare for Experimental Animals of Henan University School of Medicine (HUSOM-2017-191) in compliance with the Experimental Animal Regulations formulated by the National Science and Technology Commission, China.
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Zhang, Q., Gao, Y., Zhang, Y. et al. Cystathionine γ-lyase mediates cell proliferation, migration, and invasion of nasopharyngeal carcinoma. Oncogene 41, 5238–5252 (2022). https://doi.org/10.1038/s41388-022-02512-6