CXCR4 suppression attenuates EGFRvIII-mediated invasion and induces p38 MAPK-dependent protein trafficking and degradation of EGFRvIII in breast cancer cells.

CXCR4 suppression attenuates EGFRvIII-mediated invasion and induces p38 MAPK-dependent protein trafficking and degradation of EGFRvIII in breast cancer cells.
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DOI:
10.1016/j.canlet.2011.02.024
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发表时间:
2011-07-01
期刊:
影响因子:
9.7
通讯作者:
Tang, Careen K.
Tang, Careen K.
中科院分区:
医学1区
文献类型:
--
作者:
Rahimi, Massod;Toth, Theodore A.;Tang, Careen K.

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我们之前的报告显示,组成型激活的EGFR变体EGFRvIII上调乳腺癌细胞中促转移趋化因子受体CXCR4。在此,我们评估了在表达egfrviii的乳腺癌细胞中沉默CXCR4表达的生物学效应和细胞信号效应。短发夹RNA (Short hairpin RNA, shRNA)介导的CXCR4表达抑制显著降低了表达egfrviii的乳腺癌细胞的侵袭潜能和增殖。由于蛋白质降解增加和蛋白质运输改变,这些细胞表现出EGFRvIII活性和蛋白质表达的降低。综上所述,抑制CXCR4可抑制egfrviii介导的乳腺癌细胞侵袭和增殖。
Our previous report has shown that the constitutively activated EGFR variant, EGFRvIII, up-regulates the pro-metastatic chemokine receptor CXCR4 in breast cancer cells. Here we evaluated the biological effect and cell signaling effects of silencing CXCR4 expression in EGFRvIII-expressing breast cancer cells. Short hairpin RNA (shRNA)-mediated suppression of CXCR4 expression significantly reduced the invasive potential and proliferation of EGFRvIII-expressing breast cancer cells. These cells exhibited a reduction of EGFRvIII activity and protein expression due to increased protein degradation and altered protein trafficking. In conclusion, suppression of CXCR4 inhibits EGFRvIII-mediated breast cancer cell invasion and proliferation.
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