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Janus激酶3通过影响钙池操纵性钙通道促进乳腺癌细胞的迁移

刘夏^1,2, 魏婷^1,2, 高招娣^1,2, 赵修粱^1,2, 吴慧晴^1,2, 严静^1,2,*

¹济宁医学院基础医学院生理学教研室，济宁 272067；²新乡医学院基础医学院生理学与神经生物学教研室，新乡 453003

摘要

本研旨在探讨Janus激酶3 (JAK3)对乳腺癌细胞迁移能力的影响以及其作用机制。利用siRNA (siJAK3)沉默乳腺癌MCF-7细胞JAK3的表达，用划痕实验检测细胞迁移能力，用荧光钙成像技术检测钙池操纵性钙通道(store-operated calcium channel, SOCC)活性，用Western blot和RT-PCR检测钙池操纵性钙内流(store-operated calcium entry, SOCE)过程中的重要分子Orai1和STIM1表达水平。结果显示，SOCC抑制剂2-APB对MCF-7细胞的迁移能力有抑制作用。siJAK3转染可显著抑制MCF-7细胞的迁移能力，降低SOCC活性，下调Orai1和STIM1的mRNA和蛋白表达水平。在JAK3沉默细胞中过表达Orai1或STIM1，可使MCF-7细胞迁移力恢复。上述结果提示，JAK3通过影响SOCC促进乳腺癌细胞的迁移。

关键词： Ca2+; 钙池操纵性钙内流; Orai1; Janus激酶3

分类号：R332;R363.2;R329.2

Janus kinase 3 facilitates the migration of breast cancer cells by store-operated calcium channel

LIU Xia^1,2, WEI Ting^1,2, GAO Zhao-Di^1,2, ZHAO Xiu-Liang^1,2, WU Hui-Qing^1,2, YAN Jing^1,2,*

¹Department of Physiology, Institute of Basic Medicine, Jining Medical University, Jining 272067, China；²Department of Physiology, Institute of Basic Medicine, Xinxiang Medical University, Xinxiang 453003, China

Abstract

The present study was aimed to investigate the effect of Janus kinase 3 (JAK3) on the migration of breast cancer cells and the underlying mechanism. The expression of JAK3 in breast cancer MCF-7 cells was silenced by siRNA (siJAK3). The migration ability of MCF-7 cells was detected by scratch test. The activity of store-operated calcium channel (SOCC) was detected by fluorescence calcium imaging. The expression levels of Orai1 and STIM1, key molecules in the process of store-operated calcium entry (SOCE) were detected by Western blot and RT-PCR. The results showed that 2-APB, an inhibitor of SOCC, could inhibit the migration ability of MCF-7 cells. siJAK3 transfection significantly inhibited the migration ability of MCF-7 cells, decreased the activity of SOCC, and down-regulated mRNA and protein expression levels of Orai1 and Stim1. Over-expression of Orai1 or STIM1 in JAK3-silenced cells restored their migration ability. These results suggest that JAK3 facilitates the migration of breast cancer cells by SOCC.

Key words: Ca2+; store-operated calcium entry; Orai1; Janus kinase 3

收稿日期：2019-02-06　　录用日期：2019-07-01

通讯作者：严静　　E-mail: yanjing102@mail.jnmc.edu.cn

DOI: 10.13294/j.aps.2019.0075

引用本文：

刘夏, 魏婷, 高招娣, 赵修粱, 吴慧晴, 严静. Janus激酶3通过影响钙池操纵性钙通道促进乳腺癌细胞的迁移[J]. 生理学报 2019; 71 (6): 874-882.

LIU Xia, WEI Ting, GAO Zhao-Di, ZHAO Xiu-Liang, WU Hui-Qing, YAN Jing. Janus kinase 3 facilitates the migration of breast cancer cells by store-operated calcium channel. Acta Physiol Sin 2019; 71 (6): 874-882 (in Chinese with English abstract).