Premium
Elevation of SHARPIN Protein Levels in Prostate Adenocarcinomas Promotes Metastasis and Impairs Patient Survivals
Author(s) -
Huang Hai,
Du Tao,
Zhang Yiming,
Lai Yiming,
Li Kaiwen,
Fan Xinxing,
Zhu Dingjun,
Lin Tianxin,
Xu Kewei,
Huang Jian,
Liu Leyuan,
Guo Zhenghui
Publication year - 2017
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.23302
Subject(s) - du145 , prostate cancer , metastasis , cancer research , lncap , angiogenesis , cancer , prostate , biology , carcinogenesis , protein kinase b , medicine , pathology , apoptosis , biochemistry
BACKGROUND SHARPIN, SHANK‐associated RH domain interacting protein, associates with a linear ubiquitin chain assembly complex (LUBAC) to regulate inflammation and immunity. It has been reported that SHARPIN is highly expressed in several human tumors including ovarian cancer and liver cancer. We found that SHARPIN is also highly expressed in prostate cancer cell lines of DU145, LNCAP, and PC‐3. Suppression of SHARPIN caused an inhibition of NF‐κB signal and decreases in tumorigenesis of cultured cells in NOD/SCID mouse model. Overexpression of SHARPIN in prostate cancer cells promoted cell growth and reduced apoptosis through NF‐kB/ERK/Akt pathway and apoptosis‐associated proteins. METHODS We analyzed the expression of SHARPIN in prostate cancer tissues from 95 patients and its relationship with other clinical characteristics associated with PCA malignancies and patient survivals, and examined the impacts of SHARPIN suppression with siRNA on proliferation, angiogenesis, invasion, and expression levels of MMP‐9 of prostate cancer cells and metastasis to lung by these cells in nude mice. RESULTS High levels of SHARPIN were associated with high malignancies of PCA and predicted shorter survivals of PCA patients. Suppression of SHARPIN impaired cell proliferation, angiogenesis, and invasion and reduced levels of MMP‐9 in prostate cancer cells and reduced the size of metastatic lung tumors induced by these cells in mice. CONCLUSIONS SHARPIN enhances the metastasis of prostate cancer and impair patient survivals. Prostate 77:718–728, 2017 . © 2017 Wiley Periodicals, Inc.