Cell Engineering Research Centre and Department of Cell Biology, State Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an 710032, China.
Cell Biol Int. 2013 Jul;37(7):643-52. doi: 10.1002/cbin.10062. Epub 2013 Apr 23.
Calpains are a conserved family of calcium-dependent cysteine proteinases involved in various cellular functions. Two ubiquitous isoforms, µ- 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 µ- 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 µ- 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 µ- and m-calpain expressions also significantly attenuated MMP-2 and MMP-9 secretion. Thus µ- 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.
钙蛋白酶是一类保守的依赖钙离子的半胱氨酸蛋白水解酶家族，参与多种细胞功能。两种普遍存在的同工型 µ-和 m-钙蛋白酶是钙蛋白酶家族的关键成员，在调节细胞迁移和侵袭中发挥重要作用。然而，它们是否参与肝细胞癌（HCC）的进展尚不清楚。在这里，我们研究了 µ-和 m-钙蛋白酶在人肝癌细胞侵袭和转移过程中的功能。我们的结果表明，与正常肝细胞相比， HCC 细胞中钙蛋白酶的表达水平升高。我们的结果表明，小干扰 RNA（siRNA）介导的 µ-和 m-钙蛋白酶表达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）是恶性肿瘤侵袭和转移的关键调节剂。siRNA 介导的 µ-和 m-钙蛋白酶表达下调也显著减弱了 MMP-2 和 MMP-9 的分泌。因此，µ-和 m-钙蛋白酶可能在人肝癌细胞的侵袭和转移中发挥重要作用，钙蛋白酶可能是预防 HCC 转移的药物靶点。
