Elevation of SHARPIN Protein Levels in Prostate Adenocarcinomas Promotes Metastasis and Impairs Patient Survivals

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.

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.

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.

SHARPIN enhances the metastasis of prostate cancer and impair patient survivals. Prostate. © 2017 Wiley Periodicals, Inc.

The Prostate. 2017 Feb 23 [Epub ahead of print]

Hai Huang, Tao Du, Yiming Zhang, Yiming Lai, Kaiwen Li, Xinxing Fan, Dingjun Zhu, Tianxin Lin, Kewei Xu, Jian Huang, Leyuan Liu, Zhenghui Guo

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.