The putative tumor suppressor VILIP-1 counteracts epidermal growth factor-induced epidermal-mesenchymal transition in squamous carcinoma cells.
The putative tumor suppressor VILIP-1 counteracts epidermal growth factor-induced epidermal-mesenchymal transition in squamous carcinoma cells.
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DOI：
10.1371/journal.pone.0033116
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Braunewell KH
中科院分区：
文献类型：
--
作者：
Schönrath K;Klein-Szanto AJ;Braunewell KH
上皮-间质转化（EMT）是肿瘤细胞获得侵袭性的关键步骤。表皮生长因子（EGF）治疗鳞状细胞癌（SCC）细胞引起谱系标志物表达的变化，形态学变化，以及更高的侵袭和转移潜力。在这里，我们表明，慢性刺激与EGF诱导EMT皮肤来源的SCC细胞系沿着下调上皮标志物E-钙粘蛋白，和假定的肿瘤抑制因子VILIP-1（视色素样蛋白1）。在食管鳞状细胞癌和非小细胞肺癌中，VILIP-1的缺失与增强的侵袭性相关的临床病理特征相关。VILIP-1先前已显示在鼠SCC模型中通过增强cAMP信号传导来抑制肿瘤细胞侵袭。在小鼠皮肤SCC细胞系中，VILIP-1阴性肿瘤细胞具有低cAMP水平，而VILIP-1阳性SCC具有高cAMP水平，但具有低侵袭性。我们发现，在VILIP-1阴性SCC中，参与EMT的转录抑制因子Snail 1上调。在VILIP-1阴性的SCC细胞中，VILIP-1的异位表达降低了Snail 1的表达，而一般腺苷酸环化酶抑制剂2′，3 ′-二脱氧腺苷的应用减弱了这种作用。相反，VILIP-1阳性SCC细胞的EGF刺激导致VILIP-1的下调和Snail 1表达的诱导。Snail的诱导被升高的cAMP水平抑制。cAMP在EMT中的作用通过其对VILIP-1阳性SCC细胞中EGF诱导的迁移增强的抑制作用而进一步突出。这些结果表明，VILIP-1参与EMT的SCC通过调节转录因子蜗牛1 cAMP依赖性的方式。
Epithelial-mesenchymal transition (EMT) is a crucial step for the acquisition of invasive properties of carcinoma cells during tumor progression. Epidermal growth factor (EGF)-treatment of squamous cell carcinoma (SCC) cells provokes changes in the expression of lineage markers, morphological changes, and a higher invasive and metastatic potential. Here we show that chronic stimulation with EGF induces EMT in skin-derived SCC cell lines along with the down-regulation of the epithelial marker E-cadherin, and of the putative tumor suppressor VILIP-1 (visinin-like protein 1). In esophageal squamous cell carcinoma and non-small cell lung carcinoma the loss of VILIP-1 correlates with clinicopathological features related to enhanced invasiveness. VILIP-1 has previously been shown to suppress tumor cell invasion via enhancing cAMP-signaling in a murine SCC model. In mouse skin SCC cell lines the VILIP-1-negative tumor cells have low cAMP levels, whereas VILIP-1-positive SCCs possess high cAMP levels, but low invasive properties. We show that in VILIP-1-negative SCCs, Snail1, a transcriptional repressor involved in EMT, is up-regulated. Snail1 expression is reduced by ectopic VILIP-1-expression in VILIP-1-negative SCC cells, and application of the general adenylyl cyclase inhibitor 2′,3′-dideoxyadenosine attenuated this effect. Conversely, EGF-stimulation of VILIP-1-positive SCC cells leads to the down-regulation of VILIP-1 and the induction of Snail1 expression. The induction of Snail is inhibited by elevated cAMP levels. The role of cAMP in EMT was further highlighted by its suppressive effect on the EGF-induced enhancement of migration in VILIP-1-positive SCC cells. These findings indicate that VILIP-1 is involved in EMT of SCC by regulating the transcription factor Snail1 in a cAMP-dependent manner.
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影响因子：
3.4
作者：
Karmakar, S;Das, C
通讯作者：
Das, C
影响因子：
7.5
作者：
Deeb, G;Wang, JM;Tan, DF
通讯作者：
Tan, DF
DOI：
10.1186/bcr778
发表时间：
2004
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Brown KA;Aakre ME;Gorska AE;Price JO;Eltom SE;Pietenpol JA;Moses HL
通讯作者：
Moses HL
影响因子：
8
作者：
Gan, Y.;Shi, C.;Huang, Y.
通讯作者：
Huang, Y.
影响因子：
6.7
作者：
Hayashi, Hideki;Sudo, Toshiki
通讯作者：
Sudo, Toshiki