The down-regulation of NLK expression may play a role in the proliferation, apoptosis, and invasion of laryngeal carcinoma cells and it is possible by regulating MMP-9 and CDCP1 expression.
A reporter assay showed increased luciferase activity in NLK knockdown glioma cells and transcriptional activity of β-cantenin/TCF was remarkably enhanced, which further confirmed that NLK antagonizes Wnt signaling-mediated anchorage-dependent and independent cell proliferation and invasion.
NLK expression was found to be significantly higher in CRC tissues as well as associated with the depth of tumor invasion, lymph node metastasis, distant metastasis, histological differentiation, vascular invasion and advanced tumor stage.
In vitro, we also found that NLK suppressed the biological behaviors of colorectal cancer cells, including the abilities of cell proliferation, clone formation, wound healing, migration and invasion (P<0.05), while overexpression of NLK increased the apoptotic rate of colorectal cancer cells.
Our findings show that CACNA2D3-mediated increase in intracellular calcium (Ca2+) can induce mitochondrial-mediated apoptosis and activation of NLK (through the Wnt/Ca2+ pathway) to antagonize Wnt signaling-mediated anchorage-dependent and independent cell proliferation (via CCND1 and CMYC), invasion (via MMP7) and epithelial-to-mesynchemal transition (via SNAIL).