Astrocytic laminin-211 drives disseminated breast tumor cell dormancy in brain.
Astrocytic laminin-211 drives disseminated breast tumor cell dormancy in brain.
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DOI：
10.1038/s43018-021-00297-3
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发表时间：
2022-01
期刊：
影响因子：
22.7
通讯作者：
Ghajar, Cyrus M.
中科院分区：
文献类型：
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作者：
Dai, Jinxiang;Cimino, Patrick J.;Gouin, Kenneth H. I. I. I. I. I. I.;Grzelak, Candice A.;Barrett, Alexander;Lim, Andrea R.;Long, Annalyssa;Weaver, Stephanie;Saldin, Lindsey T.;Uzamere, Aiyedun;Schulte, Vera;Clegg, Nigel;Pisarsky, Laura;Lyden, David;Bissell, Mina J.;Knott, Simon;Welm, Alana L.;Bielas, Jason H.;Hansen, Kirk C.;Winkler, Frank;Holland, Eric C.;Ghajar, Cyrus M.
虽然休眠被认为在乳腺肿瘤细胞向脑转移中起关键作用，但我们对调节该器官中播散性肿瘤细胞（DTC）休眠的分子机制的认识是有限的。在这里，使用休眠和转移性三阴性乳腺癌细胞系的连续活体成像，我们确定从单细胞或微转移状态逃逸为脑转移的限速步骤。我们发现，每一个DTC占据一个血管龛，静态DTC居住在星形胶质细胞endfeet。在这些位点，星形胶质细胞沉积的层粘连蛋白-211通过诱导肌营养不良蛋白聚糖受体与yes相关蛋白（雅普）结合，从而将其与细胞核隔离并阻止其促转移功能，从而驱动DTC静止。这些发现确定了DTC休眠的脑特异性机制，并强调需要更深入地了解肿瘤休眠，以开发预防脑转移的治疗方法。Ghajar及其同事报道，星形胶质细胞沉积的层粘连蛋白-211促进脑中播散性肿瘤细胞的静止，其方式依赖于肌营养不良蛋白聚糖对雅普的细胞质隔离。
Although dormancy is thought to play a key role in the metastasis of breast tumor cells to the brain, our knowledge of the molecular mechanisms regulating disseminated tumour cell (DTC) dormancy in this organ is limited. Here, using serial intravital imaging of dormant and metastatic triple-negative breast cancer lines, we identify escape from the single-cell or micro-metastatic state as the rate limiting step towards brain metastasis. We show that every DTC occupies a vascular niche, with quiescent DTCs residing on astrocyte endfeet. At these sites, astrocyte-deposited laminin-211 drives DTC quiescence by inducing the dystroglycan receptor to associate with yes-associated protein (YAP), thereby sequestering it from the nucleus and preventing its pro-metastatic functions. These findings identify a brain-specific mechanism of DTC dormancy and highlight the need for a more thorough understanding of tumor dormancy to develop therapeutic approaches that prevent brain metastasis. Ghajar and colleagues report that astrocyte-deposited laminin-211 promotes the quiescence of disseminated tumor cells in the brain, in a manner dependent on the cytoplasmic sequestration of YAP by dystroglycan.
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DOI：
10.1126/science.aao4227
发表时间：
2018-09-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Albrengues J;Shields MA;Ng D;Park CG;Ambrico A;Poindexter ME;Upadhyay P;Uyeminami DL;Pommier A;Küttner V;Bružas E;Maiorino L;Bautista C;Carmona EM;Gimotty PA;Fearon DT;Chang K;Lyons SK;Pinkerton KE;Trotman LC;Goldberg MS;Yeh JT;Egeblad M
通讯作者：
Egeblad M
影响因子：
21.3
作者：
Er EE;Valiente M;Ganesh K;Zou Y;Agrawal S;Hu J;Griscom B;Rosenblum M;Boire A;Brogi E;Giancotti FG;Schachner M;Malladi S;Massagué J
通讯作者：
Massagué J
影响因子：
4
作者：
Gumbiner, Barry M.;Kim, Nam-Gyun
通讯作者：
Kim, Nam-Gyun
影响因子：
46.9
作者：
Fredriksson, S;Gullberg, M;Landegren, U
通讯作者：
Landegren, U
影响因子：
21.3
作者：
通讯作者：
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