TRIM27/MRTF-B-Dependent Integrin β1 Expression Defines Leading Cells in Cancer Cell Collectives
TRIM27/MRTF-B-Dependent Integrin β1 Expression Defines Leading Cells in Cancer Cell Collectives
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DOI：
10.1016/j.celrep.2014.03.068
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发表时间：
2014-05-01
期刊：
影响因子：
8.8
通讯作者：
Takahashi, Masahide
中科院分区：
文献类型：
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作者：
Kato, Takuya;Enomoto, Atsushi;Takahashi, Masahide
对于集体侵袭，癌细胞形成由最前面的领先细胞(LCS)和后面的跟随细胞(FCS)组成的紧密联系的群体。然而，定义LCS和FCS的分子机制仍然难以捉摸。在这里，我们证明了LCS，而不是FCS，在细胞间黏附丧失后上调了整合素β1的表达。整合素β1的LC特异性表达是由TRIM27/MRTF-B复合体转录后调节的，以响应细胞间黏附的丧失，从而通过microRNA-124调节整合素β1mRNA在LC中的稳定性和翻译。因此，缺失TRIM27和MRTF-B基因可抑制LCS中整合素β1的上调，并阻断肿瘤细胞群在体内外的侵袭。因此，我们的发现揭示了LCS的特定功能是由与细胞自由表面的存在相关的内在机制所定义的，这为调节肿瘤内异质性提供了洞察力。
For collective invasion, cancer cells form cohesive groups comprised of leading cells (LCs) at the forefront and following cells (FCs) at the rear. However, the molecular mechanisms that define LCs and FCs remain elusive. Here, we demonstrated that LCs, but not FCs, upregulated the expression of integrin beta 1 after the loss of intercellular adhesion. The LC-specific expression of integrin beta 1 was posttranscriptionally regulated by the TRIM27/MRTF-B complex in response to the loss of intercellular adhesion, thereby regulating the stability and translation of integrin beta 1 mRNA via microRNA-124 in LCs. Accordingly, depletion of TRIM27 and MRTF-B abrogated the upregulation of integrin beta 1 in LCs and blocked the invasion of cancer cell groups in vitro and in vivo. Therefore, our findings revealed that the specific function of LCs was defined by intrinsic mechanisms related to the presence of the cell's free surface, providing insights into the regulation of intratumor heterogeneity.