Abnormal activation of the Wnt3a/β-catenin signaling pathway promotes the expression of TBX3 and the EMT pathway to mediate the occurrence of adenomyosis

Abstract Background TBX3 is a transcription factor that can regulate cell proliferation, apoptosis, invasion, and migration in different tumor cells; however, its role in adenomyosis (ADM) has not been previously studied. Some of ADM’s pathophysiological characteristics are similar to those of malignant tumors (e.g., abnormal proliferation, migration, and invasion). Methods and results we hypothesized that TBX3 might have a role in ADM. We used tamoxifen-induced ICR mice to establish ADM disease model. The study procedure included western blotting and immunohistochemistry to analyze protein levels; additionally, we used intraperitoneal injection of Wnt/β-catenin pathway inhibitor XAV-939 to study the relationship between TBX3 and Wnt/β-catenin pathway as well as PCNA and TUNEL to detect cell proliferation and apoptosis, respectively. TBX3 overexpression and epithelial-to-mesenchymal transition (EMT) in ADM mice was found to be associated with activation of the Wnt3a/β-catenin pathway. Treatment with XAV-939 in ADM mice led to the inhibition of both TBX3 and EMT; moreover, abnormal cell proliferation was suppressed, the depth of invasion of endometrium cells was limited and the expression of ERα was suppressed. Thus, the use of XAV-939 effectively inhibited further invasion of endometrial cells. Conclusion These findings suggest that TBX3 may play an important role in the development of ADM. The expression of TBX3 in ADM was regulated by the Wnt3a/β-catenin pathway. The activation of the Wnt3a/β-catenin pathway in ADM promoted TBX3 and ERα expression and induced the occurrence of EMT, thus promoting cell proliferation and inhibiting apoptosis, ultimately accelerating the development of ADM. The study provides a reference for the diagnosis of ADM