CNN1 regulates the DKK1/Wnt/β-catenin/c-myc signaling pathway by activating TIMP2 to inhibit the invasion, migration and EMT of lung squamous cell carcinoma cells.

The present study aimed to investigate the effect of calponin 1 (CNN1) on the invasion and migration of lung squamous cell carcinoma (LUSC) cells and the associations between CNN1, tissue inhibitor of metalloproteinases 2 (TIMP2), Dickkopf-1 (DKK1) and the Wnt/β-catenin/c-myc signaling pathway. The expression levels of CNN1 and TIMP2 in LUSC cells and the association between CNN1 and TIMP2 were predicted using the GEPIA database. The cells were transiently transfected to overexpress CNN1, which resulted in inhibition of DKK1 and TIMP2 expression levels. Wound healing and Transwell assays were used to detect the invasive and migratory abilities of LUSC cells. Reverse transcription-quantitative PCR and western blotting were used to investigate the expression levels of CNN1, MMP2, MMP9, E-cadherin, N-cadherin (N-cad), SLUG, DKK1, β-catenin and c-myc. The expression levels of N-cad were detected using immunofluorescence staining. The results indicated that overexpression of CNN1 inhibited the invasion and migration of NCI-H2170 cells. Inhibition of DKK1 reversed this change and the expression levels of β-catenin and c-myc were upregulated, whereas the expression levels of DKK1 were downregulated with a concomitant inhibition of TIMP2. In summary, these results demonstrated that CNN1 regulated the DKK1/Wnt/β-catenin/c-myc signaling pathway by activating TIMP2 to inhibit the invasion, migration and epithelial-to-mesenchymal transition of LUSC cells.