Zhang Deng-Yong, Sun Wan-Liang, Ma Xiang, Zhang Pei, Wu Wei, Wu Huan, Zhou Shuo, Lu Zheng
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical College Bengbu, Anhui, China.
Department of Pharmacy, Bengbu Medical College Bengbu, Anhui, China.
Int J Clin Exp Pathol. 2017 Oct 1;10(10):10325-10333. eCollection 2017.
Patients with hepatocellular carcinoma (HCC) have a poor survival rate because of its high invasion ability. Therefore, it is necessary to elucidate the mechanisms of HCC migration and invasion. Our previous study showed that follistatin-like 5 (FSTL5), which was associated with the prognosis of HCC patients, acts as an inhibitor of HCC cell proliferation. It also promotes the transition of cell morphology from mesenchymal to epithelial, which is associated with the process of mesenchymal-to-epithelial transition. In this study, we used two HCC cell lines (SK-Hep1 and SMMC-7721) to explore the effect of FSTL5 on HCC invasion and migration. We found that up-regulated FSTL5 restrained HCC invasion and migration by transwell, wound healing, detachment, and attachment assays. Decreased expression of YAP was found upon over-expression of FSTL5, as well as inhibition of the Wnt/β-catenin signaling pathway. YAP is a downstream gene of the Wnt/β-catenin signaling pathway and plays an important role in HCC metastasis. Thus, we speculate that FSTL5 inhibits the invasion of HCC through the Wnt/β-catenin/YAP pathway. In conclusion, FSTL5 exerts an inhibitory effect on HCC metastasis and proliferation through the Wnt/β-catenin/YAP pathway and may be a target gene for anti-tumor therapy.
肝细胞癌（HCC）患者由于其高侵袭能力而生存率较低。因此，有必要阐明HCC迁移和侵袭的机制。我们之前的研究表明，与HCC患者预后相关的卵泡抑素样5（FSTL5）可作为HCC细胞增殖的抑制剂。它还促进细胞形态从间充质向上皮的转变，这与间充质向上皮转变的过程相关。在本研究中，我们使用两种HCC细胞系（SK-Hep1和SMMC-7721）来探究FSTL5对HCC侵袭和迁移的影响。我们发现，通过Transwell、伤口愈合、脱离和附着实验，上调的FSTL5抑制了HCC的侵袭和迁移。FSTL5过表达时，YAP表达降低，同时Wnt/β-连环蛋白信号通路受到抑制。YAP是Wnt/β-连环蛋白信号通路的下游基因，在HCC转移中起重要作用。因此，我们推测FSTL5通过Wnt/β-连环蛋白/YAP途径抑制HCC的侵袭。总之，FSTL5通过Wnt/β-连环蛋白/YAP途径对HCC转移和增殖发挥抑制作用，可能是抗肿瘤治疗的靶基因。
