Rap1GAP regulates renal cell carcinoma invasion.
Rap1GAP regulates renal cell carcinoma invasion.
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DOI：
10.1016/j.canlet.2012.01.022
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发表时间：
2012-07-01
期刊：
影响因子：
9.7
通讯作者：
Daaka, Yehia
中科院分区：
文献类型：
--
作者：
Kim, Wan-Ju;Gersey, Zachary;Daaka, Yehia
虽然局部和区域性肾肿瘤患者的生存率较高，但转移性疾病患者的死亡率显著增加。因此，研究肾癌细胞迁移和侵袭的分子机制，为晚期肾癌患者提供有效的治疗方法是十分必要的。Rap 1是一种小的GT3蛋白，与癌细胞的生长和侵袭有关。在这里，我们分析了常用的肾细胞癌（RCC）细胞系的迁移和侵袭特性，并将其与Rap灭活剂Rap 1GAP的表达和功能相关联。我们报告Rap 1GAP水平与侵袭呈负相关，但与迁移无关。我们还报道了Rap 1GAP的强制过表达降低了RCC细胞的侵袭，但不影响其增殖速率。Rap 1GAP在RCC细胞中的低表达水平至少部分是由于启动子超甲基化。用去甲基化药物地西他滨（5-azadC）拯救Rap 1GAP的表达，降低了RCC SN 12 C细胞对胶原、纤连蛋白和基质胶基质的侵袭。RCC细胞系表达不同水平的细胞粘附蛋白，并且Rap 1GAP的强制过表达减弱了已知调节癌细胞侵袭的钙粘蛋白和整合素的水平。这些结果表明，Rap 1GAP表达的靶向恢复可能作为一种潜在的治疗方法，以减少肾癌的转移。
Although patients with localized and regional kidney tumors have a high survival rate, incidence of mortality significantly increases for patients with metastatic disease. It is imperative to decipher the molecular mechanisms of kidney tumor migration and invasion in order to develop effective therapies for patients with advanced cancer. Rap1, a small GTPase protein, has been implicated in cancer cell growth and invasion. Here, we profile migratory and invasive properties of commonly used renal cell carcinoma (RCC) cell lines and correlate that with expression and function of the Rap inactivator Rap1GAP. We report that levels of Rap1GAP inversely correlate with invasion but not migration. We also report that forced over-expression of Rap1GAP decreases invasion of RCC cells but does not impact their rate of proliferation. Low expression levels of Rap1GAP in RCC cells are due, at least in part, to promoter hypermethylation. Rescued expression of Rap1GAP with a demethylating drug, decitabine (5-azadC), decreases the RCC SN12C cell invasion of collagen, fibronectin, and Matrigel matrices. RCC cell lines express distinct levels of cell adhesion proteins and the forced over-expression of Rap1GAP attenuated levels of both cadherins and integrins that are known to regulate the cancer cells invasion. These results demonstrate that targeted restoration of Rap1GAP expression may serve as a potential therapeutic approach to reduce metastasis of kidney cancers.
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影响因子：
5.3
作者：
Tsygankova, Oxana A.;Prendergast, Gregory V.;Meinkoth, Judy L.
通讯作者：
Meinkoth, Judy L.
影响因子：
6
作者：
Zhang, ZC;Mitra, RS;D'Silva, NJ
通讯作者：
D'Silva, NJ
影响因子：
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作者：
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通讯作者：
Patard, Jean-Jacques
影响因子：
7.5
作者：
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通讯作者：
Takeichi, Masatoshi
DOI：
10.1083/jcb.108.6.2435
发表时间：
1989-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Behrens J;Mareel MM;Van Roy FM;Birchmeier W
通讯作者：
Birchmeier W