Abstract:
Objective To investigate the expression of calcium/calmodulin-dependent protein kinase II (CaMKⅡ) in lung adenocarcinoma and determine its role in lung adenocarcinoma invasion and metastasis.
Methods The relationship between the expression of CaMKⅡ and clinicopathological parameters of patients with lung adenocarcinoma was analyzed using immunohistochemistry (IHC) staining of paraffin-embedded tissue sections. Concurrently, the expression of CaMKⅡ in lung adenocarcinoma and its paired lymph node metastases was compared, paraffin tissue samples from 113 patients with lung adenocarcinoma and 21 matched primary and lymph node metastases were collected from patients with lung adenocarcinoma who underwent surgical treatment in Tianjin Medical University Cancer Institute & Hospital from January to December 2011. The H1299 and Calu3 lung adenocarcinoma cell lines were transfected lentivirus with the high expression CaMKⅡ vector in the experimental group and negative control vector in the control group. Invasion and metastasis of the lung adenocarcinoma cells were investigated using Transwell and scratch tests, respectively. The relationship between CaMKⅡ expression and epithelial–mesenchymal transformation (EMT) and the activation of the epidermal growth factor receptor (EGFR) pathway was detected using Western blot.
Results Clinicopathological analysis revealed that the expression of CaMKⅡ was positively correlated with TNM stage and lymph node metastasis of lung adenocarcinoma. The expression of CaMKⅡ in lung adenocarcinoma with lymph node metastasis was significantly higher than that in the primary tumor (P<0.05). In vitro experiments showed that the number of transmembrane lung adenocarcinoma cells with increased CaMKⅡ expression was significantly elevated and the wound healing ability was enhanced. The level of phosphorylated-CaMKⅡ increased after the activation of the EGFR pathway, and CaMKⅡ promoted the expression of EMT-related proteins and transcription factors.
Conclusions CaMKⅡ participates in EGFR signal transduction, promotes the EMT process, and increases the invasion and metastasis abilities of lung adenocarcinoma cells.