Exosome transfer from stromal to breast cancer cells regulates therapy resistance pathways.
Exosome transfer from stromal to breast cancer cells regulates therapy resistance pathways.
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DOI：
10.1016/j.cell.2014.09.051
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发表时间：
2014-10-23
期刊：
影响因子：
64.5
通讯作者：
Minn AJ
中科院分区：
文献类型：
--
作者：
Boelens MC;Wu TJ;Nabet BY;Xu B;Qiu Y;Yoon T;Azzam DJ;Twyman-Saint Victor C;Wiemann BZ;Ishwaran H;Ter Brugge PJ;Jonkers J;Slingerland J;Minn AJ
与癌细胞的基质通讯可以影响治疗反应。我们发现，间质和乳腺癌（BrCa）细胞利用旁分泌和旁分泌信号来驱动化疗和放射抵抗。在异型相互作用后，外泌体从基质转移到BrCa细胞。外泌体内的RNA，主要是非编码转录物和转座因子，刺激模式识别受体RIG-I以激活STAT 1依赖性抗病毒信号传导。同时，基质细胞也激活BrCa细胞上的NOTCH 3。旁分泌抗病毒和旁分泌N 0 TCH 3途径会聚，因为STAT 1促进对N 0 TCH 3的转录应答并扩增治疗抗性肿瘤起始细胞。主要的人类和/或小鼠BrCa分析支持抗病毒/NOTCH 3途径在NOTCH信号传导和基质介导的抗性中的作用，其通过与γ分泌酶抑制剂的组合治疗而消除。因此，基质细胞通过利用外泌体来激发抗病毒信号传导而与BrCa细胞协调复杂的串扰。这扩大了擅长抵抗治疗和重新启动肿瘤生长的BrCa亚群。
Stromal communication with cancer cells can influence treatment response. We show that stromal and breast cancer (BrCa) cells utilize paracrine and juxtacrine signaling to drive chemotherapy and radiation resistance. Upon heterotypic interaction, exosomes are transferred from stromal to BrCa cells. RNA within exosomes, which are largely non-coding transcripts and transposable elements, stimulates the pattern recognition receptor RIG-I to activate STAT1-dependent anti-viral signaling. In parallel, stromal cells also activate NOTCH3 on BrCa cells. The paracrine anti-viral and juxtacrine NOTCH3 pathways converge as STAT1 facilitates transcriptional responses to NOTCH3 and expands therapy resistant tumor-initiating cells. Primary human and/or mouse BrCa analysis support the role of anti-viral/NOTCH3 pathways in NOTCH signaling and stroma-mediated resistance, which is abrogated by combination therapy with gamma secretase inhibitors. Thus, stromal cells orchestrate an intricate cross-talk with BrCa cells by utilizing exosomes to instigate anti-viral signaling. This expands BrCa subpopulations adept at resisting therapy and re-initiating tumor growth.
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RIG-I 样受体的免疫信号传导。
影响因子：
32.4
作者：
Loo YM;Gale M Jr
通讯作者：
Gale M Jr
影响因子：
14.5
作者：
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通讯作者：
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影响因子：
4.4
作者：
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通讯作者：
Ishwaran, Hemant
DOI：
10.1073/pnas.1209414109
发表时间：
2012-07-31
影响因子：
11.1
作者：
Fabbri, Muller;Paone, Alessio;Croce, Carlo M.
通讯作者：
Croce, Carlo M.
影响因子：
64.5
作者：
Luga, Valbona;Zhang, Liang;Wrana, Jeffrey L.
通讯作者：
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