SUMO-specific protease 1 promotes prostate cancer progression and metastasis.
SUMO-specific protease 1 (SENP1) is a member of de-SUMOylation protease family and has an important role in the regulation of androgen receptor-dependent transcription and hypoxia signaling. This activity profile of SENP1 prompted us to investigate whether SENP1 is involved in the pathogenesis of prostate cancer. In previous studies, we have detected the overexpression of SENP1 in both precancerous prostate intraepithelial neoplasia (PIN) lesions and prostate cancer tissue samples from patients. Whereas our whole-animal model has demonstrated that SENP1 induction is critical for prostate cell transformation, the role of SENP1 in prostate cancer progression is still unknown. In this study, we show that SENP1 expression directly correlates with prostate cancer aggressiveness and reccurrence, by analyzing more than 150 prostate cancer specimens. Modulating SENP1 level dictates colony formation of prostate cancer cell lines, tumor growth in nude mice and also prostate cancer cell migration and invasion. Silencing SENP1 level in highly metastatic prostate cancer cells perturbs their ability to metastasize to the bone and initiates secondary tumors. Mechanistically, the expression of two critical bone remodeling proteins, matrix metalloproteinase 2 (MMP2) and MMP9, is regulated by SENP1 through the HIF1α signaling pathway. All these results show the contribution of SENP1 to the progression of prostate cancer, and suggest that SENP1 may be a prognostic marker and a therapeutic target for metastasis in prostate cancer patients.
The Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Q
Q
Wang
N
N
Xia
T
T
Li
Y
Y
Xu
Y
Y
Zou
Y
Y
Zuo
Q
Q
Fan
T
T
Bawa-Khalfe
E T H
ET
Yeh
J
J
Cheng
D000818:Animals; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D003546:Cysteine Endopeptidases; D018450:Disease Progression; D010450:Endopeptidases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014162:Transfection
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010450:Endopeptidases; C404512:SENP1 protein, human; D003546:Cysteine Endopeptidases