C Zhang1, C Li2, X Chen2, Y Zhou2, B Yin1, R Ni3, Y Zhang4, J Liu5. 1. Grade 14, Clinical Medicine, Medical College, Nantong University, Nantong, 226001, Jiangsu, People's Republic of China. 2. Department of Hepatic Oncology, Affiliated Cancer Hospital of Nantong University, 30# Tong Yang Road, Nantong, 226361, Jiangsu, People's Republic of China. 3. Department of Gastroenterology, Affiliated Hospital of Nantong University, 20# Xisi Road, Nantong, 226001, Jiangsu, People's Republic of China. 4. Department of Hepatic Oncology, Affiliated Cancer Hospital of Nantong University, 30# Tong Yang Road, Nantong, 226361, Jiangsu, People's Republic of China. Zhangyixinnt@yeah.net. 5. Department of Gastroenterology, Affiliated Hospital of Nantong University, 20# Xisi Road, Nantong, 226001, Jiangsu, People's Republic of China. liujinxia1985@yeah.net.
Abstract
PURPOSE: Although hepatocellular carcinoma (HCC) is one of the most common malignant tumors, its molecular mechanism is still unknown. Dishevelled 2 (Dvl2) is one of the downstream targets of non-canonical Wnt signaling, which has been demonstrated to be of great importance in the progression of cancers. Nevertheless, the expression mechanisms and physiological significance of Dvl2 in HCC remain unclear. METHODS: Western blotting and immunohistochemistry were used to measure Dvl2 protein expression in HCC and adjacent normal tissues of 101 patients. Wound healing and transwell assays were used to determine cell migration and invasion. RESULTS: Dvl2 expression was upregulated in HCC tissues compared to the adjacent normal tissues. Moreover, its expression level was significantly correlated with histological grade (P = 0.042), metastasis (P = 0.005) and vein invasion (P = 0.009) in patients with HCC. Wound healing and transwell assays showed that knockdown of Dvl2 reduced cell migration and invasion in HepG2 cells. Finally, we confirmed that Dvl2 could regulate the migration and invasion of HCC cells by interacting with P62 in non-canonical Wnt signaling. CONCLUSIONS: Our data showed that Dvl2 was overexpressed in HCC tissues and was also correlated with poor prognosis, suggesting that Dvl2 is a novel therapeutic target for HCC.
PURPOSE: Although hepatocellular carcinoma (HCC) is one of the most common malignant tumors, its molecular mechanism is still unknown. Dishevelled 2 (Dvl2) is one of the downstream targets of non-canonical Wnt signaling, which has been demonstrated to be of great importance in the progression of cancers. Nevertheless, the expression mechanisms and physiological significance of Dvl2 in HCC remain unclear. METHODS: Western blotting and immunohistochemistry were used to measure Dvl2 protein expression in HCC and adjacent normal tissues of 101 patients. Wound healing and transwell assays were used to determine cell migration and invasion. RESULTS:Dvl2 expression was upregulated in HCC tissues compared to the adjacent normal tissues. Moreover, its expression level was significantly correlated with histological grade (P = 0.042), metastasis (P = 0.005) and vein invasion (P = 0.009) in patients with HCC. Wound healing and transwell assays showed that knockdown of Dvl2 reduced cell migration and invasion in HepG2 cells. Finally, we confirmed that Dvl2 could regulate the migration and invasion of HCC cells by interacting with P62 in non-canonical Wnt signaling. CONCLUSIONS: Our data showed that Dvl2 was overexpressed in HCC tissues and was also correlated with poor prognosis, suggesting that Dvl2 is a novel therapeutic target for HCC.
Authors: M J Smalley; E Sara; H Paterson; S Naylor; D Cook; H Jayatilake; L G Fryer; L Hutchinson; M J Fry; T C Dale Journal: EMBO J Date: 1999-05-17 Impact factor: 11.598