Grade 14, Clinical Medicine, Medical College, Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.
Department of Hepatic Oncology, Affiliated Cancer Hospital of Nantong University, 30# Tong Yang Road, Nantong, 226361, Jiangsu, People's Republic of China.
Clin Transl Oncol. 2017 Dec;19(12):1507-1517. doi: 10.1007/s12094-017-1697-z. Epub 2017 Jun 6.
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.
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.
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.
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.
尽管肝细胞癌 (HCC) 是最常见的恶性肿瘤之一，但它的分子机制仍不清楚。Dvl2 是非经典 Wnt 信号的下游靶标之一，其在癌症进展中具有重要作用。然而，Dvl2 在 HCC 中的表达机制和生理意义尚不清楚。
采用 Western blot 和免疫组织化学法检测 101 例 HCC 患者及其癌旁正常组织中 Dvl2 蛋白的表达。划痕愈合和 Transwell 实验用于测定细胞迁移和侵袭。
与癌旁正常组织相比，Dvl2 在 HCC 组织中表达上调。此外，其表达水平与 HCC 患者的组织学分级（P=0.042）、转移（P=0.005）和静脉侵犯（P=0.009）显著相关。划痕愈合和 Transwell 实验表明，Dvl2 敲低可降低 HepG2 细胞的迁移和侵袭。最后，我们证实 Dvl2 可以通过与非经典 Wnt 信号中的 P62 相互作用来调节 HCC 细胞的迁移和侵袭。
我们的数据表明，Dvl2 在 HCC 组织中过度表达，且与不良预后相关，表明 Dvl2 是 HCC 的一个新的治疗靶点。
