Oncotarget

Research Papers:

PPA1 regulates tumor malignant potential and clinical outcome of colon adenocarcinoma through JNK pathways

Ping Wang, Yi Zhou, Qi Mei, Jing Zhao, Liu Huang and Qiang Fu _

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Oncotarget. 2017; 8:58611-58624. https://doi.org/10.18632/oncotarget.17381

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Abstract

Ping Wang1,3*, Yi Zhou2,*, Qi Mei1, Jing Zhao1, Liu Huang1 and Qiang Fu1

1Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China

2Department of Gastrointestinal Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China

3Department of Oncology, Huanggang Central Hospital, Huanggang, Hubei, 438000, China

*These authors have contributed equally to this work

Correspondence to:

Qiang Fu, email: fqfqfuqiang@gmail.com

Keywords: colon cancer, JNK, PPA1, prognosis, proliferation

Received: December 20, 2016    Accepted: March 27, 2017    Published: April 24, 2017

ABSTRACT

Colorectal cancer (CRC) represents one of the most prevalent malignancies and the third leading cause of cancer death worldwide. Inorganic pyrophosphatase (PPA1) is an enzyme that catalyzes the hydrolysis of pyrophosphate to inorganic phosphate, therefore participates in the energy metabolism. Proteomic studies have demonstrated the up-regulated expression of PPA1 in various tumors, however, its expression pattern in CRC hasn’t been reported. In the current study, we used RT-qCR, Western Blot and immunohistochemical (IHC) staining to explore the expression of PPA1 in 113 paired colon cancer tissues and adjacent normal tissues, which revealed that PPA1 was correlated with lymph node metastasis. The prognostic value of PPA1 was confirmed by Kaplan-Meier survival analysis and Cox regression analysis. We further purified PPA1 and obtained the phosphor-JNK1 protein and performed enzymatic studies, which identified that PPA1 can directly dephosphorylate pJNK1, while showed no catalytic activity towards pERK or p-p38 proteins. Moreover, overexpression of PPA1 enhanced cell viability through JNK-p53 signaling pathways, and it may also prevent cell apoptosis by inhibiting Bcl-2 and Caspase-3 cleavage. To our knowledge, this is the first study demonstrated the expression and clinical significance of PPA1 in colon cancer, which also provided evidence that figuring out PPA1 specific inhibitors can be invaluable in the future chemotherapy development towards colon cancer.


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