Department of Pathology, Tianjin Medical University, Tianjin, China.
J Cell Mol Med. 2011 Mar;15(3):691-700. doi: 10.1111/j.1582-4934.2010.01052.x.
E-cadherin loss is a key biological mechanism in tumour invasion. As a main regulator of epithelial-mesenchymal transition (EMT) mechanism-mediated invasion and metastasis, Twist1 plays an important role through its regulation of E-cadherin expression. However, whether or not Twist2 has the same function in tumour metastasis remains unclear. The purpose of this study is to investigate the expressions and different roles of Twist1 and Twist2 in human hepatocellular carcinoma (HCC). The expressions of Twist1 and Twist2 in HCC tissue were evaluated by immunohistochemical staining. The role of Twist1 and Twist2 in invasiveness was also evaluated in vitro by using HCC cell lines. Twist1 nuclear overexpression is found to be correlated with HCC metastasis, and its expression is negatively correlated with E-cadherin expression in human tissue. Twist2, a Twist1 homology protein, only expresses in the cytoplasm and shows no significant correlation with HCC metastasis. By ectopic transfection of Twist1 and Twist2 into the HCC cells, HepG2 and PLC, Twist1 is able to down-regulate E-cadherin expression and promote matrix metalloproteinase (MMP) activation, specifically in MMP2 and MMP9. In functional assays, Twist1 is found to promote invasion in HepG2 and PLC cells, but the invasion ability of the groups is not affected Twist2. Our findings indicate that Twist1 induces HCC invasion via increased activity in MMPs, leading to poor clinical prognoses. The results of this study also demonstrate a novel cogitation in Twist2, which has no effect on HCC invasion and metastasis. Twist1 may contribute to HCC invasion and metastasis and may be used as a novel therapeutic target for the inhibition of HCC metastasis.
E-钙黏蛋白的丢失是肿瘤侵袭的一个关键生物学机制。作为上皮-间质转化（EMT）机制介导的侵袭和转移的主要调节因子，Twist1 通过调节 E-钙黏蛋白的表达发挥重要作用。然而，Twist2 是否在肿瘤转移中具有相同的功能尚不清楚。本研究旨在探讨 Twist1 和 Twist2 在人肝细胞癌（HCC）中的表达及其不同作用。通过免疫组织化学染色评估 HCC 组织中 Twist1 和 Twist2 的表达。还通过使用 HCC 细胞系在体外评估 Twist1 和 Twist2 在侵袭性中的作用。发现 Twist1 核过表达与 HCC 转移相关，其表达与人组织中的 E-钙黏蛋白表达呈负相关。Twist2 是 Twist1 的同源蛋白，仅在细胞质中表达，与 HCC 转移无明显相关性。通过将 Twist1 和 Twist2 异位转染到 HCC 细胞 HepG2 和 PLC 中，Twist1 能够下调 E-钙黏蛋白的表达并促进基质金属蛋白酶（MMP）的激活，特别是 MMP2 和 MMP9。在功能测定中，发现 Twist1 促进 HepG2 和 PLC 细胞的侵袭，但 Twist2 对这些细胞侵袭能力没有影响。我们的研究结果表明，Twist1 通过增加 MMP 的活性诱导 HCC 侵袭，导致不良的临床预后。本研究的结果还表明 Twist2 具有新的作用，即对 HCC 侵袭和转移没有影响。Twist1 可能有助于 HCC 的侵袭和转移，可作为抑制 HCC 转移的新的治疗靶点。
