SDF-1/CXCR4 axis promotes the growth and sphere formation of hypoxic breast cancer SP cells by c-Jun/ABCG2 pathway
SDF-1/CXCR4 axis promotes the growth and sphere formation of hypoxic breast cancer SP cells by c-Jun/ABCG2 pathway
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SDF-1/CXCR4轴通过c-Jun/ABCG2通路促进缺氧乳腺癌SP细胞的生长和球形形成
DOI：
10.1016/j.bbrc.2018.09.130
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发表时间：
2018-10-28
影响因子：
3.1
通讯作者：
Ge, Guanqun
中科院分区：
文献类型：
--
作者：
He, Chenyang;Zhang, Huimin;Ge, Guanqun
ATP结合盒亚家族G成员2（ABCG 2）赋予侧群（SP）细胞的主要表型，即癌症干细胞样细胞。在本研究中，SP细胞显示出明显较高的ABCG 2表达水平，球形成效率（SFE）和生长速度，即使在缺氧条件下。pcDNA-CXCR 4转染后，CXCR 4过表达可显著增加ABCG 2的表达，并促进缺氧SP细胞的SFE和生长，而CXCR 4抑制剂AMD 3100可抑制这种促进作用。此外，我们发现CXCR 4促进c-Jun的表达，c-Jun是致癌JNK/c-Jun通路中的主要基因。我们的电泳迁移率变动分析（EMSA）和染色质免疫沉淀（ChIP）分析的数据都表明，c-Jun直接结合ABCG 2启动子序列。此外，JNK/c-Jun过表达促进ABCG 2表达，SFE和缺氧SP细胞的生长，并且c-Jun抑制剂SP 600125可以挽救这种促进作用。总之，CXCR 4通过c-Jun介导的ABCG 2转录激活增加缺氧条件下乳腺癌SP细胞的生长和SFE。(C)2018爱思唯尔公司All rights reserved.
ATP-binding cassette sub-family G member 2 (ABCG2) confers to the major phenotypes of side population (SP) cells, the cancer stem-like cells. In this study, the SP cells displayed a distinctly higher ABCG2 expression level, sphere formation efficiency (SFE) and growth rate even under hypoxia condition. CXCR4 overexpression by pcDNA-CXCR4 transfection robustly increased ABCG2 expression, and promoted SFE and growth of hypoxic SP cells, while CXCR4 inhibitor AMD3100 could suppress the promotion. Additionally, we found that CXCR4 promoted the expression of c-Jun, a major gene in the oncogenic JNK/c-Jun pathway. Our data on electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assays both showed that c-Jun directly bound with the ABCG2 promoter sequence. Moreover, overexpression of JNK/c-Jun promoted ABCG2 expression, SFE, and growth of hypoxic SP cells and the promotion could be rescued by c-Jun inhibitor SP600125. In conclusion, CXCR4 increases the growth and SFE of breast cancer SP cells under hypoxia through c-Jun-mediated transcriptional activation of ABCG2. (C) 2018 Elsevier Inc. All rights reserved.