NF-κB and MMP-2 expression regulated by Lrig1 through the MEK-ERK signaling pathway in Hazaks' esophageal squamous cell carcinoma北大核心CSCD

Objective: This work aimed to investigate the expression levels of Lrig1, NF-κB, and MMP-2 in Hazak's esophageal squamous cell carcinoma (ESCC), as well as to explore the relationship of Lrig1 expression through the PI3K-AKT and MEK-ERK signaling pathways with clinicopathological indices. Methods: First, RT-PCR analysis was performed to study the expression levels of Lrig1, NF-κB, and MMP-2 in 48 ESCC and noncancerous specimens. Second, some key genes of the PI3K and MEK signaling pathways such as PI3K, AKT1, MEK1, MEK2, MEK5, ERK1, and ERK2 were detected in Lrig1-positive and -negative tissues to identify the possible signaling pathway of Lrig1-regulated NF-κB and MMP-2 expression. Results: The expression of NF-κB (P<0.001, P=0.014) and MMP-2 (P=0.003, P=0.045) was significantly correlated with Lrig1 in cancer and distal normal tissues. Lrig1 may be negatively correlated with NF-κB and MMP-2 at the protein level. MEK5 (P<0.001) and ERK2 (P=0.009) expression was associated with Lrig1 in cancer tissues. PI3K expression was correlated with Lrig1 in the distal normal tissues (P<0.001). The coordinate expression ratio of Lrig1 to NF-κB and MMP2 reached 52.1% (25/48). This co-expression may be related to lymph node metastasis (P=0.020) but not to other clinicopathological features. Conclusions: These findings suggest that MMP-2 and NF-κB expression is related to Lrig1 in Hazak's ESCC, and that MEK and ERK2 mRNA expression are related to Lrig1. The co-expression of NF-κB, MMP-2, and Lrig1 may promote lymph node metastasis in ESCC among Hazak people. Lrig1 may regulate the expression of target genes not through the PI3K-AKT pathway but through the MEK-ERK signaling pathway. Further related studies are needed in the future.