Cathepsin D enhances breast cancer invasion and metastasis through promoting hepsin ubiquitin-proteasome degradation
Cathepsin D enhances breast cancer invasion and metastasis through promoting hepsin ubiquitin-proteasome degradation
复制标题
组织蛋白酶 D 通过促进 hepsin 泛素蛋白酶体降解增强乳腺癌侵袭和转移
DOI：
10.1016/j.canlet.2018.09.021
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发表时间：
2018
期刊：
影响因子：
9.7
通讯作者：
Song Shushu
中科院分区：
文献类型：
--
作者：
Zhang Chunyi;Zhang Mingming;Song Shushu
Hepsin是正常形态的生长和维持以及细胞运动和发育、血液凝固和促炎免疫应答的启动所必需的。组织蛋白酶D（Cathepsin D，CtsD）作为一种新的蛋白质参与了Hepsin的调控。CtsD通过促进乳腺癌细胞中hepsin的泛素化和随后的蛋白酶体降解使其不稳定。乳腺癌组织芯片免疫组化结果也表明hepsin表达与CtsD呈负相关。CtsD过表达可通过增强细胞间粘附分子-1（ICAM-1）的表达促进乳腺癌细胞的迁移、侵袭和转移。异位hepsin表达抑制这些作用。综上所述，我们的数据揭示了一个关键的CtsD-hepsin信号轴在迁移和转移，这可能有助于更好地了解乳腺癌进展中的功能和分子机制。
Hepsin is required for the growth and maintenance of normal morphology, as well as for cell motility and development, initiation of blood coagulation and pro-inflammatory immune response. Here we showed that Cathepsin D (CtsD) as a novel protein is involved in the regulation of hepsin. CtsD destabilizes hepsin by promoting its ubiquitylation and subsequent proteasomal degradation in breast cancer cells. Breast cancer tissue microarray also indicated that hepsin expression was negatively correlated with CtsD by immunohistochemistry. Overexpression of CtsD promoted breast cancer cell migration, invasion and metastasis by enhancing the expression of intercellular cell adhesion molecule-1 (ICAM-1)in vitroandin vivo. These effects were inhibited by ectopic hepsin expression. Taken together, our data reveal a critical CtsD-hepsin signaling axis in migration and metastasis, which may contribute to a better understanding of the function and molecular mechanism in breast cancer progression.