title: Elevation of SHARPIN Protein Levels in Prostate Adenocarcinomas Promotes Metastasis and Impairs Patient Survivals.
abstract: 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.
authors.affiliation: Department of Urology, The Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.|Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.|Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M University, Houston, Texas.
authors.forename: Hai
authors.initials: H
authors.lastname: Huang
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.|Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M University, Houston, Texas.|Department of Gynecology & Obstetrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Du
authors.affiliation: Department of Urology, The Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.|Department of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Urology, The Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Lai
authors.affiliation: Department of Urology, The Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Kaiwen
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Urology, The Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xinxing
authors.initials: X
authors.lastname: Fan
authors.affiliation: Department of Urology, The Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Dingjun
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Department of Urology, The Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.|Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Tianxin
authors.initials: T
authors.lastname: Lin
authors.affiliation: Department of Urology, The Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Kewei
authors.initials: K
authors.lastname: Xu
authors.affiliation: Department of Urology, The Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
authors.affiliation: Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M University, Houston, Texas.|Department of Molecular and Cellular Medicine, College of Medicine, Texas A&M University, College Station, Houston, Texas.
authors.forename: Leyuan
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Urology, The Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Zhenghui
authors.initials: Z
authors.lastname: Guo
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000368:Aged; D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016019:Survival Analysis; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C575183:SHARPIN protein, human; C554944:Sipl1 protein, mouse; D014452:Ubiquitins; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: MMP-2; MMP-9; SHARPIN; invasion; migration