Caveolin-1 Inhibits Proliferation, Migration, and Invasion of Human Colorectal Cancer Cells by Suppressing Phosphorylation of Epidermal Growth Factor Receptor
Juanli Yang, Tienian Zhu, Ruijing Zhao, Dongmei Gao, Yujie Cui, Kun Wang, Yanli Guo
Department of Pain and Rehabilitation, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China (mainland)
Med Sci Monit 2018; 24:332-341
Although downregulation of caveolin-1 (Cav-1), which is a key constituent of membrane caveolae and a regulator of cellular processes, is associated with colorectal cancer (CRC), its involvement in the disease progression is largely unknown. This study aimed to explore the role of Cav-1 in CRC and the associated mechanisms.
MATERIAL AND METHODS: Fresh tissues from patients with CRC and human CRC SW480 cells were used to evaluate Cav-1 and Ki-67 expression using immunohistochemistry and Western blotting. The MTS and Transwell assays were performed to determine the effects of Cav-1 overexpression via pcDNA3.1/Cav-1 plasmid on cell proliferation and metastasis. The effect of Cav-1 on the epidermal growth factor receptor (EGFR) activation was evaluated by Western blotting. The correlation of Cav-1 expression with clinicopathological factors was statistically analyzed.
RESULTS: Overexpression of Cav-1 significantly reduced proliferation, migration, and invasion of SW480 cancer cells in vitro. The EGF-induced phosphorylation of EGFR and activations of the RAF-MEK-ERK and PI3K-AKT pathways were adversely regulated by Cav-1 overexpression in vitro. In 76 cases of CRC patients with EGFR expression, a negative correlation was observed between the level of Cav-1 and tumor-node-metastasis stage, lymph node metastasis, and distant metastasis (All p<0.05). Finally, the expression level of Cav-1 was negatively correlated with that of Ki-67.
CONCLUSIONS: This report is the first to show that overexpression of Cav-1significantly inhibits the proliferation, migration, and invasion potential of SW480 cells, possibly through reducing EGF-induced EGFR activation. High Cav-1 expression level may be a predictor of positive outcomes in patients with colorectal cancer.
Keywords: Caveolin 1, Cell Proliferation, Colorectal Neoplasms, Receptor, Epidermal Growth Factor, Tumor Suppressor Proteins