PA28α/β Promote Breast Cancer Cell Invasion and Metastasis via Down-Regulation of CDK15
PA28α/β Promote Breast Cancer Cell Invasion and Metastasis via Down-Regulation of CDK15
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PA28α/β 通过下调 CDK15 促进乳腺癌细胞侵袭和转移
DOI：
10.3389/fonc.2019.01283
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发表时间：
2019-11-22
影响因子：
4.7
通讯作者：
Shi, Jian
中科院分区：
文献类型：
--
作者：
Li, Shengnan;Dai, Xiaoqin;Shi, Jian
PA 28 α/β激活的免疫蛋白酶体经常参与MHC I类抗原的加工，然而，它是否参与乳腺肿瘤的进展仍不清楚。在这里，我们的证据表明，PA 28 α/β蛋白负责乳腺癌细胞的迁移，侵袭和转移。免疫蛋白酶体核心亚基β 5i的敲低也强烈抑制肿瘤细胞迁移和侵袭。有趣的是，PA 28 α/β和β 5i的沉默上调了细胞周期蛋白依赖性激酶15（CDK 15）的蛋白表达。我们的数据进一步表明CDK 15的丢失对于乳腺肿瘤细胞的侵袭和转移是重要的。总之，这项研究表明，靶向PA 28 α/β是治疗转移性乳腺癌的一种潜在方法。
PA28 alpha/beta activated immunoproteasome frequently participates in MHC class I antigen processing, however, whether it is involved in breast tumor progression remains largely unclear. Here, our evidences show that PA28 alpha/beta proteins are responsible for breast cancer cell migration, invasion, and metastasis. Knockdown of immunoproteasome core subunit beta 5i also robustly suppresses the tumor cell migration and invasion. Interestingly, silencing of PA28 alpha/beta and beta 5i up-regulates the protein expression of cyclin-dependent kinase 15 (CDK15). Our data further indicate that the loss of CDK15 is important for breast tumor cell invasion and metastasis. Taken together, this study implicates that targeting of PA28 alpha/beta represents a potential way for treatment of metastatic breast cancer.