Oncotarget

Research Papers:

PTRF suppresses the progression of colorectal cancers

Fengyun Wang, Yongqiu Zheng, Matthew Orange, Chunlin Yang, Bin Yang, Jiong Liu, Tao Tan, Xiangxue Ma, Tin Chen, Xiaolan Yin, Xudong Tang and Hua Zhu _

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Oncotarget. 2017; 8:48650-48659. https://doi.org/10.18632/oncotarget.9424

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Abstract

Fengyun Wang1,*, Yongqiu Zheng2,*, Matthew Orange3,*, Chunlin Yang4, Bin Yang1, Jiong Liu1, Tao Tan4, Xiangxue Ma1, Tin Chen1, Xiaolan Yin1, Xudong Tang1 and Hua Zhu4

1 Gastroenterology Department, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China

2 Institute of Basic Medical Sciences of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China

3 Department of Physical Education and Human Performance, Central Connecticut State University, New Britain, CT, USA

4 Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, USA

*: These authors have contributed equally to this work

Correspondence to:

Hua Zhu, email:

Xudong Tang, email:

Yongqiu Zheng, email:

Keywords: PTRF, mTOR, colorectal cancer, progression

Received: March 07, 2016 Accepted: April 11, 2016 Published: May 18, 2016

Abstract

As a key component of caveolae structure on the plasma membrane, accumulated evidence has suggested that Polymerase I and Transcript Release Factor (PTRF) plays a pivotal role in suppressing the progression of human malignances. However, the function of PTRF in the development of colorectal cancers is still unclear. Here we report that the expression of PTRF is significantly reduced in tumor tissues derived from human patients with colorectal cancers, and that the downregulation of PTRF correlates to the advanced stage of the disease. In addition, we found that the expression of PTRF negatively regulates the tumorigenic activities of colorectal cell lines (Colo320, HT29 and CaCo2). Furthermore, ectopic PTRF expression caused significant suppression of cellular proliferation, and anchorage-independent colony growth of Colo320 cells, which have the lowest expression level of PTRF in the three studied cell lines. Meanwhile, shRNA mediated knockdown of PTRF in CaCo2 cells significantly promoted cellular proliferation and anchorage-independent colony growth. In addition, in vivo assays further revealed that tumor growth was significantly inhibited in xenografts with ectopic PTRF expression as compared to untreated Colo320 cells, but was markedly enhanced in PTRF knockdown CaCo2 cells. Biochemical studies revealed that overexpression of PTRF led to the suppression of the AKT/mTOR pathway, as evidenced by reduced phosphorylation of AKT, mTOR, and downstream MMP-9. Thus, these findings, for the first time, demonstrated that PTRF inhibits the tumorigenesis of colorectal cancers and that it might serve as a potential therapeutic target for human colon cancer patients.


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