Oncotarget

Research Papers:

ARF1 promotes prostate tumorigenesis via targeting oncogenic MAPK signaling

Jason E. Davis _, Xiayang Xie, Jianhui Guo, Wei Huang, Wen-Ming Chu, Shuang Huang, Yong Teng and Guangyu Wu

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Oncotarget. 2016; 7:39834-39845. https://doi.org/10.18632/oncotarget.9405

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Abstract

Jason E. Davis1, Xiayang Xie2, Jianhui Guo1, Wei Huang1, Wen-Ming Chu3, Shuang Huang2, Yong Teng2,4, Guangyu Wu1

1Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, Augusta, GA, USA

2Cancer Center, Augusta University, Augusta, GA, USA

3Cancer Biology Program, University of Hawaii Cancer Center, Honolulu, HI, USA

4Department of Oral Biology, Dental College of Georgia, Augusta University, Augusta, GA, USA

Correspondence to:

Guangyu Wu, email: guwu@augusta.edu

Yong Teng, email: yteng@augusta.edu

Keywords: ARF1, prostate cancer, cell growth, tumorigenesis, Raf1/MEK/ERK1/2

Received: April 16, 2014     Accepted: March 11, 2016     Published: May 17, 2016

ABSTRACT

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.


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