title: Tumor suppressor PRSS8 targets Sphk1/S1P/Stat3/Akt signaling in colorectal cancer.
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.
authors.affiliation: Department of Pathology and Institute of Precision Medicine, Jining Medical University, Jining 272067, China.
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Bao
authors.affiliation: Department of Pathology, The First Affiliated Hospital, Xinxiang Medical University, Xinxiang 453003, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Pathology and Institute of Precision Medicine, Jining Medical University, Jining 272067, China.
authors.forename: Yongchen
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Immunology, Xinxiang Medical University, Xinxiang 453003, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital, Xinxiang Medical University, Weihui 453003, China.
authors.forename: Zexin
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Pathology and Institute of Precision Medicine, Jining Medical University, Jining 272067, China.
authors.forename: Yiqiong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pathology, Xinxiang Medical University, Xinxiang 453003, China.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital, Xinxiang Medical University, Weihui 453003, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pathology, The First Affiliated Hospital, Xinxiang Medical University, Xinxiang 453003, China.|Department of Pathology, Xinxiang Medical University, Xinxiang 453003, China.
authors.forename: Weixing
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Xinxiang Medical University, Xinxiang 453003, China.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Jiwang
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Pathology, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Huali
authors.initials: H
authors.lastname: Dong
authors.affiliation: Department of Pathology, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Kui
authors.initials: K
authors.lastname: Shen
authors.affiliation: Department of Pathology, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Alan M
authors.initials: AM
authors.lastname: Diamond
authors.affiliation: Department of Pathology and Institute of Precision Medicine, Jining Medical University, Jining 272067, China.|Department of Pathology, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Wancai
authors.initials: W
authors.lastname: Yang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000236:Adenoma / Q000378:metabolism / Q000473:pathology; D000818:Animals; D063646:Carcinogenesis / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000502:physiology; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D064593:Heterografts; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008819:Mice, Nude; D043484:Proprotein Convertases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D000099271:Prostasin
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D043484:Proprotein Convertases; D051057:Proto-Oncogene Proteins c-akt; D050796:STAT3 Transcription Factor; D012697:Serine Endopeptidases; D000099271:Prostasin; C466999:SPHKAP protein, human; C494086:STAT3 protein, human; C115575:membrane-bound transcription factor peptidase, site 1
keywords: PRSS8; Sphk1; Stat3; colorectal cancer; tumor suppressor