Background: Helicobacter pylori (H. pylori) infection promotes gastric cancer (GC) through various mechanisms. It causes inflammation and damage to the gastric mucosa, thereby increasing the risk of developing GC. Sphingolipids can act as signaling molecules that activate or inhibit intracellular signaling pathways, and abnormal sphingolipid metabolism may promote tumorigenesis and metastasis. This study aimed to explore the relationship among sphingosine kinase 2 (SphK2) expression, GC progression, and H. pylori infection.
Methods: Expression profile data for SphK2 were extracted from public datasets. Normal human gastric mucosal and GC cells were co-incubated with H. pylori, and SphK2 expression in these cells was detected using western blotting. GC cells with SphK2 overexpression and knockdown were established, and the effects of SphK2 and H. pylori on the proliferation, migration, and invasion abilities of GC cells were verified using CCK-8, EdU, and Transwell assays. The expression of Ras/MEK/ERK pathway-related proteins was detected using western blotting, and the secretion of pro-inflammatory cytokines TNF-α, IL-6 and IL-1β in GC cells was detected using ELISA.
Results: SphK2 is highly expressed in GC cells and is associated with a poor prognosis. The expression of SphK2 in GC cells is related to H. pylori infection. SphK2 overexpression promotes the proliferation, migration, and invasion of GC cells and enhances the pro-inflammatory effects of H. pylori.
Conclusion: SphK2 promotes the progression of H. pylori-positive GC by activating the Ras/MEK/ERK pathway.
Keywords: Gastric cancer; Helicobacter pylori; Ras/MEK/ERK; SphK2; Sphingolipid metabolism.
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