ARF1 promotes prostate tumorigenesis via targeting oncogenic MAPK signaling.
ARF1 promotes prostate tumorigenesis via targeting oncogenic MAPK signaling.
复制标题
DOI：
10.18632/oncotarget.9405
复制
发表时间：
2016-06-28
期刊：
影响因子：
--
通讯作者：
Wu G
中科院分区：
文献类型：
--
作者：
Davis JE;Xie X;Guo J;Huang W;Chu WM;Huang S;Teng Y;Wu G
ADP-核糖基化因子1（ARF 1）是囊泡介导的膜运输的关键调节因子，并参与信号分子的激活。然而，几乎没有人知道它在前列腺癌中的功能。在这里，我们已经证明，在前列腺癌细胞和人体组织中，ARF 1的表达显著升高，并且ARF 1的表达水平与丝裂原活化蛋白激酶（MAPK）ERK 1/2的活化相关。此外，我们已经表明，过表达和敲低的ARF 1产生相反的影响，前列腺癌细胞增殖，锚定非依赖性生长和肿瘤生长的小鼠异种移植模型，ARF 1介导的细胞增殖可以消除Raf 1抑制剂GW 5074和MEK抑制剂U 0126和PD 98059。突变Thr 48可抑制ARF 1的活化，从而抑制ARF 1激活ERK 1/2和促进细胞增殖的能力。这些数据表明，前列腺癌中的异常MAPK信号传导至少部分地受ARF 1的控制，并且与Ras类似，ARF 1是前列腺癌进展中的关键调节因子。这些数据还表明，ARF 1可能是前列腺癌治疗和诊断的关键分子靶点。
ADP-ribosylation factor 1 (ARF1) is a crucial regulator in vesicle-mediated membrane trafficking and involved in the activation of signaling molecules. However, virtually nothing is known about its function in prostate cancer. Here we have demonstrated that ARF1 expression is significantly elevated in prostate cancer cells and human tissues and that the expression levels of ARF1 correlate with the activation of mitogen-activated protein kinases (MAPK) ERK1/2. Furthermore, we have shown that overexpression and knockdown of ARF1 produce opposing effects on prostate cancer cell proliferation, anchorage-independent growth and tumor growth in mouse xenograft models and that ARF1-mediated cell proliferation can be abolished by the Raf1 inhibitor GW5074 and the MEK inhibitors U0126 and PD98059. Moreover, inhibition of ARF1 activation achieved by mutating Thr48 abolishes ARF1′s abilities to activate the ERK1/2 and to promote cell proliferation. These data demonstrate that the aberrant MAPK signaling in prostate cancer is, at least in part, under the control of ARF1 and that, similar to Ras, ARF1 is a critical regulator in prostate cancer progression. These data also suggest that ARF1 may represent a key molecular target for prostate cancer therapeutics and diagnosis.
登录
查看更多内容
DOI：
10.1074/jbc.m111.316125
发表时间：
2012-02-03
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Ohashi Y;Iijima H;Yamaotsu N;Yamazaki K;Sato S;Okamura M;Sugimoto K;Dan S;Hirono S;Yamori T
通讯作者：
Yamori T
影响因子：
4.8
作者：
Lewis-Saravalli, Sebastian;Campbell, Shirley;Claing, Audrey
通讯作者：
Claing, Audrey
影响因子：
2.9
作者：
Meierhofer, Tanja;Eberhardt, Maren;Spoerner, Michael
通讯作者：
Spoerner, Michael
影响因子：
2.8
作者：
Nemoto, K;Vogt, A;Lazo, JS
通讯作者：
Lazo, JS
影响因子：
82.9
作者：
Craft, N;Shostak, Y;Sawyers, CL
通讯作者：
Sawyers, CL