Background: Helicobacter pylori  infection is recognized as a major risk factor for gastric cancer (GC) progression; however, the underlying molecular mechanisms have remained to be fully elucidated.
Methods: qPCR and Western blot were used to detect mRNA level and relative protein expression. Wound healing assay and transwell were used to determine migration and invasion of cells. Calcium imaging was used to determine calcium signaling in cells. Luciferase reporter assay and immunohistochemistry were performed.
Results: In the present study, it was demonstrated that H. pylori  infection in GC is closely associated with the depth of tumor invasion, lymph node metastasis, tumor-nodes-metastasis stage, and distant metastasis. Migration and invasion assays indicated that H. pylori  infection enhanced the migration and invasion of GC cells in a Ca²⁺-dependent manner. Calcium imaging was applied to detect intracellular Ca²⁺ and revealed that H. pylori  induced an increase of intracellular Ca²⁺ in GC cells through release from Ca²⁺ stores and extracellular Ca²⁺ influx. Further study indicated that H. pylori  infection led to an upregulation of the expression of transient receptor potential cation channel subfamily C member 6 (TRPC6) and induced an increase of Ca²⁺ through the TRPC6 channel. Furthermore, H. pylori  increased TRPC6 transcription through the Wnt/β-catenin pathway, and Wnt/β-catenin/TRPC6 signaling was identified to be at least in part responsible for H. pylori -induced GC migration and invasion. Finally, it was observed that TRPC6 expression was significantly associated with the H. pylori  infection status in GC tissues, and H. pylori  infection was associated with metastasis and poor prognosis for GC patients.
Conclusion: The present results indicate that H. pylori  causes an upregulation of TRPC6 expression through the Wnt/β-catenin pathway to promote GC progression, and this interaction may serve as a promising target for GC therapy.
Keywords: helicobacter pylori, TRPC6, Wnt/β-catenin, calcium signaling, gastric cancer