Pericyte-like spreading by disseminated cancer cells activates YAP and MRTF for metastatic colonization.
Pericyte-like spreading by disseminated cancer cells activates YAP and MRTF for metastatic colonization.
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DOI：
10.1038/s41556-018-0138-8
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发表时间：
2018-08
影响因子：
21.3
通讯作者：
Massagué J
中科院分区：
文献类型：
--
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
播散性癌细胞的转移性种植主要发生在血管周围的小生境中。在这里，我们表明，机械转导信号引发的周细胞样传播的癌细胞在宿主组织毛细血管转移定植是至关重要的。播散的癌细胞利用细胞粘附分子L1（L1 CAM）在毛细血管上扩散并激活机械转导效应物Yes相关蛋白（雅普）和肌心蛋白相关转录因子（MRTF）。这种L1 CAM介导的扩散足以取代常驻周细胞，周细胞也使用L1 CAM进行血管周围扩散。L1 CAM通过接合β1整联蛋白和整联蛋白连接激酶（ILK）激活雅普。L1 CAM-YAP信号传导使得转移起始细胞在其浸润靶器官后立即生长以及在其从休眠期退出后生长。我们的研究结果确定了一个重要的步骤，转移性定植的开始，定义其分子组成，并提供了一个解释的广泛关联L1 CAM与转移复发的临床。
Metastatic seeding by disseminated cancer cells principally occurs in perivascular niches. Here, we show that mechanotransduction signaling triggered by the pericyte-like spreading of disseminated cancer cells on host tissue capillaries is critical for metastatic colonization. Disseminated cancer cells employ cell adhesion molecule L1 (L1CAM) to spread on capillaries and activate the mechanotransduction effectors Yes-associated protein (YAP) and myocardin-related transcription factor (MRTF). This L1CAM-mediated spreading is robust enough to displace resident pericytes, which also use L1CAM for perivascular spreading. L1CAM activates YAP by engaging β1 integrin and integrin linked kinase (ILK). L1CAM-YAP signaling enables the outgrowth of metastasis-initiating cells both immediately upon their infiltration of target organs and after they exit from a period of dormancy. Our results identify an important step in the initiation of metastatic colonization, define its molecular constituents, and provide an explanation for the widespread association of L1CAM with metastatic relapse in the clinic.
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影响因子：
5.4
作者：
Ebeling, O;Duczmal, A;Altevogt, P
通讯作者：
Altevogt, P
影响因子：
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影响因子：
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影响因子：
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作者：
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通讯作者：
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