Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization.
Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization.
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miR-200s 直接靶向 Sec23a 影响癌细胞分泌组并促进转移定植
作者：
尽管miR-200s在调节E-cadherin表达和上皮-间质转化中的作用已得到证实，但其对转移定殖的影响仍存在争议。在这里，我们使用乳腺癌转移的临床和实验模型来发现miR-200s的促转移作用超出了它们对e -钙粘蛋白和上皮表型的调节。miR-200s的过表达与乳腺癌转移风险增加相关，并促进小鼠模型中的转移定殖，这些表型不能仅通过E-cadherin表达来概括。基因组学和蛋白质组学分析揭示了miR-200过表达后基因表达向高度转移细胞的整体转变。MiR-200s部分通过直接靶向Sec23a促进转移定植，而Sec23a可介导包括Igfbp4和Tinagl1在内的转移抑制蛋白的分泌，功能和临床相关研究证实了这一点。总的来说，这些发现表明miR-200s通过影响e -cadherin依赖性上皮性状和sec23a介导的肿瘤细胞分泌组，在促进转移定植方面具有多向性作用。
Although the role of miR-200s in regulating E-cadherin expression and epithelial-mesenchymal transition is well established, their influence on metastatic colonization remains controversial. Here, we use clinical and experimental models of breast cancer metastasis to discover a pro-metastatic role of miR-200s that goes beyond their regulation of E-cadherin and epithelial phenotype. Overexpression of miR-200s is associated with increased risk of metastasis in breast cancer and promotes metastatic colonization in mouse models, phenotypes that cannot be recapitulated by E-cadherin expression alone. Genomic and proteomic analyses revealed global shifts in gene expression upon miR-200 overexpression toward that of highly metastatic cells. MiR-200s promote metastatic colonization partly through direct targeting of Sec23a, which mediates secretion of metastasis suppressive proteins, including Igfbp4 and Tinagl1, as validated by functional and clinical correlation studies. Overall, these findings suggest a pleiotropic role of miR-200s in promoting metastatic colonization by influencing E-cadherin-dependent epithelial traits and Sec23a-mediated tumor cell secretome.
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影响因子：
30.8
作者：
Lang, Michael R.;Lapierre, Lynne A.;Knapik, Ela W.
通讯作者：
Knapik, Ela W.
影响因子：
11.2
作者：
Chaffer, Christine L.;Brennan, Janelle P.;Williams, Elizabeth D.
通讯作者：
Williams, Elizabeth D.
影响因子：
11.5
作者：
Nam, Eun Ji;Yoon, Heejei;Kim, Sunghoon
通讯作者：
Kim, Sunghoon
影响因子：
2.7
作者：
Chaffer, Christine L.;Thompson, Erik W.;Williams, Elizabeth D.
通讯作者：
Williams, Elizabeth D.
影响因子：
11.2
作者：
Bracken, Cameron P.;Gregory, Philip A.;Goodall, Gregory J.
通讯作者：
Goodall, Gregory J.