17 January 2018 : Laboratory Research
Caveolin-1 Inhibits Proliferation, Migration, and Invasion of Human Colorectal Cancer Cells by Suppressing Phosphorylation of Epidermal Growth Factor ReceptorJuanli Yang1BCDE, Tienian Zhu23ABCDEFG*, Ruijing Zhao2ABCDEFG, Dongmei Gao3BCE, Yujie Cui3BCD, Kun Wang4BCD, Yanli Guo5BCD
Med Sci Monit 2018; 24: LBR332-341
BACKGROUND: 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, Colorectal Neoplasms, Receptor, Epidermal Growth Factor, Tumor Suppressor Proteins
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