Keratin 6A gene silencing suppresses cell invasion and metastasis of nasopharyngeal carcinoma via the β‑catenin cascade.

Abstract

Nasopharyngeal carcinoma (NPC) is a type of head and neck cancer. This study aimed to study the mechanisms of ectopic keratin 6A (KRT6A) in NPC. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting were performed to detect KRT6A levels in NPC cell lines (C666-1, 5-8F and SUNE-1) and a nasopharyngeal epithelial cell line (NP69, as a control). After SUNE-1 NPC cells had been silenced by KRT6A, cell viability, metastasis and invasion were determined using Cell Counting Kit-8, wound healing and Transwell assays, respectively. KRT6A levels, metastasis-associated factors and the Wnt/β-catenin pathway were measured using RT-qPCR and western blotting. It was demonstrated that KRT6A was upregulated in all detected NPC cells, among which KRT6A was the highest in SUNE-1 cells. In SUNE-1 cells, cell viability was inhibited at 24 and 48 h, and that cell metastasis and invasion were demonstrated to be suppressed by KRT6A silencing. Both the mRNA and protein levels of KRT6A, matrix metalloproteinase (MMP)-2, MMP-9, β-catenin, lymphoid enhancer binding factor 1 and T-cell specific factor 4 were reduced in the small interfering (si)KRT6A group. However, the results demonstrated that the levels of epithelial-cadherin and tissue inhibitor of metalloproteinase-2 (TIMP-2) were promoted in the siKRT6A group. The activation of the Wnt/β-catenin pathway by lithium chloride reversed the effect of si-KRT6A by modulating the expression of MMP-2/9 and TIMP2. It was observed that KRT6A silencing suppressed cell invasion and metastasis of NPC via the β-catenin cascade. Together these results provide important insights into a novel approach for the diagnosis and treatment of NPC.