Abstract
BackgroundWe previously identified that Mycoplasma hyorhinis infection promotes gastric cancer cell motility. The β‐catenin signaling pathway is critical to determining malignant cancer cell phenotypes; however, the association between M hyorhinis and the β‐catenin signaling pathway is unclear.MethodsWe performed subcellular fractionation and immunofluorescence staining to observe β‐catenin accumulation in the nucleus. The expression of downstream β‐catenin genes was detected by quantitative RT‐PCR. Gastric cancer cell motility was examined by transwell chamber migration and wound healing assays, and a co‐immunoprecipitation assay was used to detect the proteins associated with the membrane protein p37 of M hyorhinis.ResultsWe found that M hyorhinis infection promoted nuclear β‐catenin accumulation and enhanced the expression of downstream β‐catenin genes. M hyorhinis‐promoted gastric cancer cell motility was counteracted by treatment with the β‐catenin inhibitor XAV939 or β‐catenin knockdown. We further detected a protein complex containing LRP6, GSK3β, and p37 in M hyorhinis‐infected cells. M hyorhinis also induced LRP6 phosphorylation in a GSK3β‐dependent fashion. Knockdown of LRP6 or GSK3β abolished M hyorhinis‐induced cell motility.ConclusionOur results reveal that the β‐catenin signaling pathway could be activated by M hyorhinis infection, thereby contributing to M hyorhinis‐induced gastric cancer cell motility.
Highlights
We previously identified that Mycoplasma hyorhinis infection promotes gastric cancer cell motility
We provide evidence to show that Wnt/β‐catenin signaling pathway activation contributes to M hyorhinis‐induced motility in gastric cancer cells
We revealed that the β‐catenin pathway plays an important role in M hyorhinis‐induced gastric cancer cell motility
Summary
Gastric cancer is a major public health problem that accounts for approximately 10% of all cancer‐related deaths worldwide. Afriat et al[9] showed that M fermentans reduces the activity of TopoI through PARP1 by MAPK activation, thereby altering cellular gene expression and conferring camptothecin resistance All these studies suggested mycoplasma infection as a possible promoting factor in cancer initiation and progression. Aberrant activation of the Wnt/β‐catenin pathway results in deregulated cell growth and malignant transformation.[10,11] This oncogenic pathway is initiated by Wnt, and in the absence of Wnt ligands, cytoplasmic β‐catenin is subjected to phosphorylation via the β‐catenin‐disrupting complex and proteolysis via the ubiquitin‐proteasome system, through which a low level of β‐catenin is maintained.[12] In the nucleus, transcription factor T‐cell factor/lymphocyte enhancer factor (TCF/LEF) binds to the metastasis inhibitor Groucho/TLE, thereby inhibiting the transactivation of downstream β‐catenin genes.[13,14] When Wnt binds to receptor LRP6 and Frizzled, it promotes DISH protein aggregation and β‐catenin destruction complex disintegration, ensuring β‐catenin accumulation, nuclear entry and downstream gene transcriptional activation.[14,15] In this study, we provide evidence to show that Wnt/β‐catenin signaling pathway activation contributes to M hyorhinis‐induced motility in gastric cancer cells
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