CTNND2 gene expression in melanoma tissues and its effects on the malignant biological functions of melanoma cells.

Abstract

Background: The catenin delta 2 (CTNND2) gene has been implicated in the progression of various cancers, but its specific role in melanoma has not yet been thoroughly investigated. This study sought to explore the expression and biological function of CTNND2 in malignant melanoma tissues to identify new targets or biomarkers for melanoma diagnosis and treatment.

Methods: Immunohistochemistry was used to examine the levels of CTNND2 in melanoma and adjacent non-tumor tissues. A Western blot analysis was performed to quantify the expression levels of CTNND2 in human immortalized keratinocytes and melanoma cell lines. The Cell Counting Kit-8 (CCK-8) assay, plate colony formation assay, cell adhesion assay, scratch test, and Transwell assay were used to assess the effects of CTNND2 knockdown on the proliferation, adhesion, migration, and invasion of melanoma cells. The Harmonizome database was used to research the biological processes (BPs) involved in CTNND2.

Results: In the melanoma tissues, CTNND2 expression was substantially upregulated and its levels were closely linked with the pathological features of patients. The CTNND2 levels were notably more increased in the melanoma cell lines than the immortalized keratinocytes. The suppression of the CTNND2 gene substantially impeded the capacity of the melanoma cells to proliferate, migrate, and invade, and also significantly decreased their potential to attach to collagen I and IV, and fibronectin. The Harmonizome database results revealed a strong correlation between the BPs controlled by CTNND2 and the focal adhesion signaling pathway of the cells. The inhibition of the CTNND2 gene in melanoma cells resulted in a significant decrease in the phosphorylation of focal adhesion kinase (FAK) and the production of paxillin protein. In the melanoma cells, the reduction of CTNND2 did not have a significant effect on the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. However, it did considerably prevent the activation of mitogen-activated extracellular signal-regulated kinase 1/2 (MEK1/2) and its downstream molecule extracellular signal-regulated protein kinase 1/2 (ERK1/2).

Conclusions: The expression of the CTNND2 gene is increased in melanoma tissues, which enhances the ability of melanoma cells to proliferate both in vivo and in vitro. Additionally, the CTNND2 gene is crucial in controlling the adhesion process of melanoma cells. This mechanism is associated with the regulation of the FAK and MEK1/2/ERK1/2 signaling pathways. Based on our findings, CTNND2 could be used as an oncogene target for melanoma and a new treatment target or diagnostic biomarker.