PKCε inhibits isolation and sternness of side population cells via the suppression of ABCB1 transporter and PI3K/Akt, MAPK/ERK signaling in renal cell carcinoma cell line 769P
PKCε inhibits isolation and sternness of side population cells via the suppression of ABCB1 transporter and PI3K/Akt, MAPK/ERK signaling in renal cell carcinoma cell line 769P
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PKC epsilon 通过抑制肾细胞癌细胞系 769P 中的 ABCB1 转运蛋白和 PI3K/Akt、MAPK/ERK 信号传导来抑制侧群细胞的分离和严格性
DOI：
10.1016/j.canlet.2016.03.041
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发表时间：
2016-06-28
期刊：
影响因子：
9.7
通讯作者：
Qiu, Shao Peng
中科院分区：
文献类型：
--
作者：
Huang, Bin;Fu, Shun Jun;Qiu, Shao Peng
蛋白激酶C β（PICCE）是PKC家族的新成员，是包括肾细胞癌（RCC）在内的多种实体瘤的转化癌基因和肿瘤生物标志物。我们从肾细胞癌769 P细胞系中分离出侧群（SP）细胞，并证明这些细胞具有肿瘤干细胞（CSC）特性。本研究通过降低769 P SP细胞中PKC β的表达，证实PKC β的缺失与769 P SP细胞中SP细胞的存在呈负相关，以探讨PKC β在769 P SP细胞癌干细胞性中的作用。PKC β的下调也以几种方式抑制分选的769 P SP细胞的CSC潜力：增殖潜力、对化疗剂的抗性和体内肿瘤形成能力。我们的研究还表明，PKC β与ABCB 1相关，这种相关性可能有助于从769 P细胞系中分离SP细胞。此外，ABCB 1的表达直接受PKC β的调节。在769 P非SP细胞中，PKC β过表达可促进AKT、STAT 3和ERK的磷酸化。总体而言，PKC β 1下调通过调节ABCB 1转运蛋白和依赖于磷酸化作用的PI 3 K/Akt、Stat 3和MAPK/ERK通路来抑制RCC 769 P SP细胞的分选和癌干细胞样表型。因此，PKC β可能是肾细胞癌干细胞发病机制中的重要介质。(C)2016爱思唯尔爱尔兰有限公司版权所有。
Protein kinase C epsilon (PICCE), a member of the novel PKC family, is known to be a transforming oncogene and tumor biomarker for many human solid cancers including renal cell carcinoma (RCC). We isolated side population (SP) cells from the RCC 769P cell line, and proved that those cells possess cancer stem cell (CSC) characteristics. In this study, to identify the function of PKC epsilon in cancer stemness of 769P SP cells, we reduced the expression of PKC epsilon in those cells, following the results demonstrated that PKC epsilon depletion had a negative correlation with the existence of SP cells in 769P cell line. Down-regulation of PKC epsilon also suppresses the CSC potential of sorted 769P SP cells in several ways: proliferation potential, resistance to chemotherapeutics and in vivo tumor formation ability. Our study also reveals that PKC epsilon is associated with ABCB1 and this association probably contributed to the SP cells isolation from 769P cell line. Furthermore, the expression of ABCB1 is directly regulated by PKC epsilon. Additionally, after the depletion of PKC epsilon, the phosphorylation of pAkt, pStat3 and pERK was apparently suppressed in 769P SP cells, whereas PKC epsilon overexpression could promote the phosphorylation of AKT, STAT3 and ERK in 769P Non SP cells. Overall, PKC epsilon down-regulation suppresses sorting and the cancer stem-like phenotype of RCC 769P SP cells through the regulation of ABCB1 transporter and the PI3K/Akt, Stat3 and MAPK/ERK pathways that are dependent on the phosphorylation effects. Thus, PKC epsilon may work as an important mediator in cancer stem cell pathogenesis of renal cell cancer. (C) 2016 Elsevier Ireland Ltd. All rights reserved.