Calpains are required for invasive and metastatic potentials of human HCC cells
Calpains are required for invasive and metastatic potentials of human HCC cells
复制标题
钙蛋白酶是人类 HCC 细胞侵袭和转移潜力所必需的
DOI：
10.1002/cbin.10062
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发表时间：
2013-07-01
影响因子：
3.9
通讯作者：
Jiang, Jian-Li
中科院分区：
文献类型：
--
作者：
Chen, Bo;Tang, Juan;Jiang, Jian-Li
钙调蛋白是一个保守的钙依赖半胱氨酸蛋白酶家族，参与多种细胞功能。两种普遍存在的亚型，u-和m-calain，是calain家族中的关键成员，在调节细胞迁移和侵袭方面发挥着重要作用。然而，目前尚不清楚它们是否参与了肝细胞癌的进展。在这里，我们研究了u-和m-calain在人肝癌细胞侵袭和转移过程中的作用。我们的研究结果表明，与正常肝细胞相比，在肝细胞癌组织中钙蛋白水解酶的表达水平升高。我们的结果表明，小干扰RNA(SiRNA)介导的u-和m-calain表达的沉默显著抑制了人肝癌细胞的黏附、迁移和侵袭潜能。基质金属蛋白酶(MMPs)是恶性肿瘤侵袭转移的关键调节因子。SiRNA介导的Mu-和m-calain表达下调也显著抑制了MMP2和MMP9的分泌。因此，u-和m-calain可能在人肝癌细胞的侵袭和转移中起重要作用，可能是预防肝细胞癌转移的药物靶点。
Calpains are a conserved family of calcium-dependent cysteine proteinases involved in various cellular functions. Two ubiquitous isoforms, mu- and m-calpain, are key members of the calpain family that play essential roles in regulating cell migration and invasion. However, it remains unclear whether they are involved in the progression of hepatocellular carcinoma (HCC). Here, we investigated the functions of mu- and m-calpain in the invasive and metastatic processes of human hepatoma cells. Our results indicated that the expression levels of calpains were elevated in HCC cells compared with those in normal hepatic cells. Our results indicated that small interfering RNA (siRNA)-mediated silencing of mu- and m-calpain expressions significantly suppressed the adhesive, migrative and invasive potentials of human hepatoma cells. The matrix metalloproteinases (MMPs) are key regulators of malignant tumour invasion and metastasis. siRNA-mediated down-regulation of mu- and m-calpain expressions also significantly attenuated MMP-2 and MMP-9 secretion. Thus mu- and m-calpain may play important roles in the invasion and metastasis of human hepatoma cells, and calpains may be drug targets for preventing HCC metastasis.