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

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...

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Bibliographic Details
Published in:Oncotarget 2016-05, Vol.7 (18), p.26780-26792
Main Authors: Bao, Yonghua, Li, Kai, Guo, Yongchen, Wang, Qian, Li, Zexin, Yang, Yiqiong, Chen, Zhiguo, Wang, Jianguo, Zhao, Weixing, Zhang, Huijuan, Chen, Jiwang, Dong, Huali, Shen, Kui, Diamond, Alan M, Yang, Wancai
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing - metabolism
Adenocarcinoma - metabolism
Adenocarcinoma - pathology
Adenoma - metabolism
Adenoma - pathology
Animals
Carcinogenesis - metabolism
Carcinogenesis - pathology
Cell Proliferation - physiology
Colorectal Neoplasms - metabolism
Colorectal Neoplasms - pathology
Heterografts
Humans
Mice
Mice, Knockout
Mice, Nude
Proprotein Convertases - metabolism
Proto-Oncogene Proteins c-akt - metabolism
Research Paper
Serine Endopeptidases - metabolism
Signal Transduction - physiology
STAT3 Transcription Factor - metabolism
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Summary: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.
ISSN:1949-2553
DOI:10.18632/oncotarget.8511