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Oncotarget. 2016 May 3;7(18):26780-92. doi: 10.18632/oncotarget.8511.

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

Author information

1
Department of Pathology and Institute of Precision Medicine, Jining Medical University, Jining 272067, China.
2
Department of Pathology, The First Affiliated Hospital, Xinxiang Medical University, Xinxiang 453003, China.
3
Department of Immunology, Xinxiang Medical University, Xinxiang 453003, China.
4
Department of Surgical Oncology, The First Affiliated Hospital, Xinxiang Medical University, Weihui 453003, China.
5
Department of Pathology, Xinxiang Medical University, Xinxiang 453003, China.
6
Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.
7
Department of Pathology, University of Illinois at Chicago, Chicago, IL 60612, USA.

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.

KEYWORDS:

PRSS8; Sphk1; Stat3; colorectal cancer; tumor suppressor

PMID:
27050145
PMCID:
PMC5042014
DOI:
10.18632/oncotarget.8511
[Indexed for MEDLINE]
Free PMC Article

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