An RNA interference phenotypic screen identifies a role for FGF signals in colon cancer progression.
An RNA interference phenotypic screen identifies a role for FGF signals in colon cancer progression.
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DOI：
10.1371/journal.pone.0023381
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Morkel M
中科院分区：
文献类型：
--
作者：
Leushacke M;Spörle R;Bernemann C;Brouwer-Lehmitz A;Fritzmann J;Theis M;Buchholz F;Herrmann BG;Morkel M
在肿瘤细胞中，信号级联的逐步致癌失调诱导细胞形态的改变，并促进恶性性状的获得。在这里，我们确定了一组21个基因，包括FGF 9，作为决定肿瘤细胞形态的RNA干扰表型筛选在SW 480结肠癌细胞。使用一组小分子抑制剂，我们随后建立了表型效应，下游信号级联，和相关的基因表达的FGF受体信号的签名。我们发现FGF信号的抑制诱导上皮细胞粘附和结肠癌细胞运动性的丧失。这些作用通过丝裂原活化蛋白激酶（MAPK）和Rho GT3级联介导。与这些发现一致，抑制MEK 1/2或JNK级联，但不抑制PI 3 K-AKT信号传导轴也诱导上皮细胞形态。最后，我们发现FGF 9在一部分晚期结肠癌中表达强烈，并且过表达与患者的生存率呈负相关。我们的功能和表达分析表明，FGF受体信号可以促进结肠癌的进展。
In tumor cells, stepwise oncogenic deregulation of signaling cascades induces alterations of cellular morphology and promotes the acquisition of malignant traits. Here, we identified a set of 21 genes, including FGF9, as determinants of tumor cell morphology by an RNA interference phenotypic screen in SW480 colon cancer cells. Using a panel of small molecular inhibitors, we subsequently established phenotypic effects, downstream signaling cascades, and associated gene expression signatures of FGF receptor signals. We found that inhibition of FGF signals induces epithelial cell adhesion and loss of motility in colon cancer cells. These effects are mediated via the mitogen-activated protein kinase (MAPK) and Rho GTPase cascades. In agreement with these findings, inhibition of the MEK1/2 or JNK cascades, but not of the PI3K-AKT signaling axis also induced epithelial cell morphology. Finally, we found that expression of FGF9 was strong in a subset of advanced colon cancers, and overexpression negatively correlated with patients' survival. Our functional and expression analyses suggest that FGF receptor signals can contribute to colon cancer progression.
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影响因子：
6.6
作者：
Fu, Yulong;Kim, Ingyu;Lian, Peiwen;Li, Ao;Zhou, Liang;Li, Cunxi;Liang, Dan;Coffey, Robert J.;Ma, Jie;Zhao, Ping;Zhan, Qimin;Wu, Guanqing
通讯作者：
Wu, Guanqing
影响因子：
10.5
作者：
Brembeck, FH;Schwarz-Romond, T;Birchmeier, W
通讯作者：
Birchmeier, W
影响因子：
2.8
作者：
Brabletz, T;Jung, A;Kirchner, T
通讯作者：
Kirchner, T
影响因子：
21.3
作者：
Batlle, E;Sancho, E;de Herreros, AG
通讯作者：
de Herreros, AG
影响因子：
29.4
作者：
DIGNASS, AU;TSUNEKAWA, S;PODOLSKY, DK
通讯作者：
PODOLSKY, DK