Open AccessTumor suppressor PRSS8 targets Sphk1/S1P/Stat3/Akt signaling in colorectal cancer
Author(s) -
Yonghua Bao,
Kai Li,
Yanning Guo,
Qian Wang,
Zexin Li,
Yuyao Yang,
Zhiguo Chen,
Jianguo Wang,
Weixing Zhao,
Huijuan Zhang,
Jiwang Chen,
Huali Dong,
Kui Shen,
Alan M. Diamond,
Wancai Yang
Publication year - 2016
Publication title -
oncotarget
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.373
H-Index - 127
ISSN - 1949-2553
DOI - 10.18632/oncotarget.8511
Subject(s) - medicine , colorectal cancer , protein kinase b , oncology , cancer , cancer research , signal transduction , biology , biochemistry
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.