Oncotarget

Research Papers:

Tumor suppressor PRSS8 targets Sphk1/S1P/Stat3/Akt signaling in colorectal cancer

Yonghua Bao, Kai Li, Yongchen Guo, Qian Wang, Zexin Li, Yiqiong Yang, Zhiguo Chen, Jianguo Wang, Weixing Zhao, Huijuan Zhang, Jiwang Chen, Huali Dong, Kui Shen, Alan M. Diamond and Wancai Yang _

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Oncotarget. 2016; 7:26780-26792. https://doi.org/10.18632/oncotarget.8511

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Abstract

Yonghua Bao1,*, Kai Li2,*, Yongchen Guo1,*, Qian Wang3, Zexin Li4, Yiqiong Yang1, Zhiguo Chen5, Jianguo Wang4, Weixing Zhao2,5, Huijuan Zhang5, Jiwang Chen6, Huali Dong7, Kui Shen7, Alan M. Diamond7, Wancai Yang1,7

1Department of Pathology and Institute of Precision Medicine, Jining Medical University, Jining 272067, China

2Department of Pathology, the First Affiliated Hospital, Xinxiang Medical University, Xinxiang 453003, China

3Department of Immunology, Xinxiang Medical University, Xinxiang 453003, China

4Department of Surgical Oncology, the First Affiliated Hospital, Xinxiang Medical University, Weihui 453003, China

5Department of Pathology, Xinxiang Medical University, Xinxiang 453003, China

6Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA

7Department of Pathology, University of Illinois at Chicago, Chicago, IL 60612, USA

*These authors have contributed equally to this work

Correspondence to:

Wancai Yang, email: [email protected]

Keywords: PRSS8, colorectal cancer, tumor suppressor, Sphk1, Stat3

Abbreviations: PRSS8, protease serine 8; Stat3, signal transducer and activator of transcription 3; Sphk1, sphingosine kinase 1; S1PR, Sphingosine-1- Phosphate receptor

Received: December 23, 2015     Accepted: March 06, 2016     Published: March 31, 2016

ABSTRACT

PRSS8 is a membrane-anchored serine protease prostasin and has been shown an association with carcinogenesis. Herein we found that PRSS8 expression was significantly reduced in colorectal adenomas and adenocarcinomas. The decreased PRSS8 was well correlated with clinical stages, poor differentiation and shorter survival time of colorectal cancer. Furthermore, increase of PRSS8 led to the inhibition of colorectal cancer cell proliferation, knockdown of PRSS8 accelerated cell proliferation in vitro, and overexpressing PRSS8 retarded cancer cell growth in nude mice. Mechanistic studies revealed that PRSS8 inhibited Sphk1/S1P/Stat3/Akt signaling pathway, in terms of inverse association between PRSS8 and Sphk1 in human colorectal cancers and in Sphk1-/- mice. In conclusion, PRSS8 acts as a tumor suppressor by inhibiting Sphk1/S1P/Stat3/Akt signaling pathway, and could be used as a biomarker to monitor colorectal carcinogenesis and predict outcomes.


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