Oncotarget

Research Papers:

Suppression of breast cancer metastasis through the inactivation of ADP-ribosylation factor 1

Xiayang Xie, Shou-Ching Tang, Yafei Cai, Wenhu Pi, Libin Deng, Guangyu Wu, Alain Chavanieu and Yong Teng _

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Oncotarget. 2016; 7:58111-58120. https://doi.org/10.18632/oncotarget.11185

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Abstract

Xiayang Xie1,2, Shou-Ching Tang3,4, Yafei Cai3, Wenhu Pi3, Libin Deng3, Guangyu Wu5, Alain Chavanieu6, Yong Teng1,3,7

1Department of Oral Biology, Augusta University, Augusta, GA, USA

2Department of Pediatrics, Emory Children’s Center, Emory University, Atlanta, GA, USA

3Georgia Cancer Center, Augusta University, Augusta, GA, USA

4Tianjin Medical University Cancer Institute and Hospital, Tianjin, P.R. China

5Department of Pharmacology and Toxicology, Augusta University, Augusta, GA, USA

6Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, Université de Montpellier, CNRS, ENSCM, France

7Department of Biochemistry and Molecular Biology, Augusta University, Augusta, GA, USA

Correspondence to:

Yong Teng, email: [email protected]

Keywords: ARF1, breast cancer, metastasis, LM11, zebrafish

Received: June 14, 2016     Accepted: August 05, 2016     Published: August 10, 2016

ABSTRACT

Metastasis is the major cause of cancer-related death in breast cancer patients, which is controlled by specific sets of genes. Targeting these genes may provide a means to delay cancer progression and allow local treatment to be more effective. We report for the first time that ADP-ribosylation factor 1 (ARF1) is the most amplified gene in ARF gene family in breast cancer, and high-level amplification of ARF1 is associated with increased mRNA expression and poor outcomes of patients with breast cancer. Knockdown of ARF1 leads to significant suppression of migration and invasion in breast cancer cells. Using the orthotopic xenograft model in NSG mice, we demonstrate that loss of ARF1 expression in breast cancer cells inhibits pulmonary metastasis. The zebrafish-metastasis model confirms that the ARF1 gene depletion suppresses breast cancer cells to metastatic disseminate throughout fish body, indicating that ARF1 is a very compelling target to limit metastasis. ARF1 function largely dependents on its activation and LM11, a cell-active inhibitor that specifically inhibits ARF1 activation through targeting the ARF1-GDP/ARNO complex at the Golgi, significantly impairs metastatic capability of breast cancer cell in zebrafish. These findings underline the importance of ARF1 in promoting metastasis and suggest that LM11 that inhibits ARF1 activation may represent a potential therapeutic approach to prevent or treat breast cancer metastasis.


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