Helicobacter pylori upregulates TRPC6 via Wnt/β-catenin signaling to promote gastric cancer migration and invasion.
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.
['Song|Yang|Y|', 'Liu|Gao|G|', 'Liu|Shuang|S|', 'Chen|Rong|R|', 'Wang|Na|N|', 'Liu|Zhaoyu|Z|', 'Zhang|Xiao|X|', 'Xiao|Zheng|Z|', 'Liu|Lin|L|']
helicobacter pylori TRPC6 Wnt/β-catenin gastric cancer calcium signaling