Epithelial-mesenchymal plasticity determines estrogen receptor positive breast cancer dormancy and epithelial reconversion drives recurrence.
Epithelial-mesenchymal plasticity determines estrogen receptor positive breast cancer dormancy and epithelial reconversion drives recurrence.
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DOI：
10.1038/s41467-022-32523-6
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发表时间：
2022-08-25
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
超过70%的人类乳腺癌（BC）是雌激素受体α阳性（ER+）。ER+ BC的临床挑战是它们可能在初始治疗后数十年复发。由于缺乏足够的体内模型，潜伏性疾病的机制仍然难以捉摸。我们比较了ER+和三阴性（TN）BC细胞的导管内异种移植物，并证明播散性TNBC细胞在原发部位的增殖与TNBC细胞相似，而播散性ER+ BC细胞增殖较慢，它们降低CDH 1并增加ZEB 1，2表达，并表现出上皮-间充质可塑性（EMP）和休眠的特征。强制E-钙粘蛋白表达克服ER+ BC休眠。细胞因子信号在更活跃与不活跃的播散性肿瘤细胞中富集，表明微环境触发觉醒。我们的结论是，导管内异种移植模型ER + BC休眠，并揭示EMP是必不可少的休眠细胞状态的产生，并从EMP的靶向出口具有治疗潜力。肿瘤休眠的研究受到合适的体内模型的限制。在此，作者表明，乳腺导管内乳腺癌（BC）异种移植模型雌激素受体α阳性（ER+）BC休眠和三阴性（TN）BC的快速转移进展特征。休眠的播散性ER+ BC细胞显示上皮-间充质可塑性的特征，并且E-钙粘蛋白的强制表达允许它们克服休眠。
More than 70% of human breast cancers (BCs) are estrogen receptor α-positive (ER+). A clinical challenge of ER+ BC is that they can recur decades after initial treatments. Mechanisms governing latent disease remain elusive due to lack of adequate in vivo models. We compare intraductal xenografts of ER+ and triple-negative (TN) BC cells and demonstrate that disseminated TNBC cells proliferate similarly as TNBC cells at the primary site whereas disseminated ER+ BC cells proliferate slower, they decrease CDH1 and increase ZEB1,2 expressions, and exhibit characteristics of epithelial-mesenchymal plasticity (EMP) and dormancy. Forced E-cadherin expression overcomes ER+ BC dormancy. Cytokine signalings are enriched in more active versus inactive disseminated tumour cells, suggesting microenvironmental triggers for awakening. We conclude that intraductal xenografts model ER + BC dormancy and reveal that EMP is essential for the generation of a dormant cell state and that targeting exit from EMP has therapeutic potential. The study of tumour dormancy is limited by suitable in vivo models. Here the authors show that mammary intraductal breast cancer (BC) xenografts model estrogen receptor α-positive (ER+) BC dormancy and rapid metastatic progression characteristic of triple-negative (TN) BC. The dormant disseminated ER+ BC cells display characteristics of epithelial-mesenchymal plasticity and forced expression of E-cadherin allows them to overcome dormancy.
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影响因子：
11.1
作者：
Kozma KJ;Done SJ;Egan SE
通讯作者：
Egan SE
影响因子：
22.7
作者：
Di Martino JS;Nobre AR;Mondal C;Taha I;Farias EF;Fertig EJ;Naba A;Aguirre-Ghiso JA;Bravo-Cordero JJ
通讯作者：
Bravo-Cordero JJ
EMT亚型影响上皮可塑性和细胞迁移模式。
影响因子：
11.8
作者：
Aiello NM;Maddipati R;Norgard RJ;Balli D;Li J;Yuan S;Yamazoe T;Black T;Sahmoud A;Furth EE;Bar-Sagi D;Stanger BZ
通讯作者：
Stanger BZ
DOI：
10.1158/1078-0432.ccr-13-2332
发表时间：
2014-04-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Jeselsohn R;Yelensky R;Buchwalter G;Frampton G;Meric-Bernstam F;Gonzalez-Angulo AM;Ferrer-Lozano J;Perez-Fidalgo JA;Cristofanilli M;Gómez H;Arteaga CL;Giltnane J;Balko JM;Cronin MT;Jarosz M;Sun J;Hawryluk M;Lipson D;Otto G;Ross JS;Dvir A;Soussan-Gutman L;Wolf I;Rubinek T;Gilmore L;Schnitt S;Come SE;Pusztai L;Stephens P;Brown M;Miller VA
通讯作者：
Miller VA
DOI：
10.1073/pnas.1705301114
发表时间：
2017-11-07
影响因子：
11.1
作者：
Herndler-Brandstetter, Dietmar;Shan, Liang;Flavell, Richard A.
通讯作者：
Flavell, Richard A.