OTUB1 de-ubiquitinating enzyme promotes prostate cancer cell invasion in vitro and tumorigenesis in vivo.

Abstract

BACKGROUND:

Ubiquitination is a highly dynamic and reversible process with a central role in cell homeostasis. Deregulation of several deubiquitinating enzymes has been linked to tumor development but their specific role in prostate cancer progression remains unexplored.

METHODS:

RNAi screening was used to investigate the role of the ovarian tumor proteases (OTU) family of deubiquitinating enzymes on the proliferation and invasion capacity of prostate cancer cells. RhoA activity was measured in relation with OTUB1 effects on prostate cancer cell invasion. Tumor xenograft mouse model with stable OTUB1 knockdown was used to investigate OTUB1 influence in tumor growth.

RESULTS:

Our RNAi screening identified OTUB1 as an important regulator of prostate cancer cell invasion through the modulation of RhoA activation. The effect of OTUB1 on RhoA activation is important for androgen-induced repression of p53 expression in prostate cancer cells. In localized prostate cancer tumors OTUB1 was found overexpressed as compared to normal prostatic epithelial cells. Prostate cancer xenografts expressing reduced levels of OTUB1 exhibit reduced tumor growth and reduced metastatic dissemination in vivo.

CONCLUSIONS:

OTUB1 mediates prostate cancer cell invasion through RhoA activation and promotes tumorigenesis in vivo. Our results suggest that drugs targeting the catalytic activity of OTUB1 could potentially be used as therapeutics for metastatic prostate cancer.

• Authors: Diego Iglesias-Gato, Yin-Choy Chuan, Ning Jiang, Charlotte Svensson, Jing Bao, Indranil Paul, Lars Egevad, Benedikt M Kessler, Pernilla Wikström, Yuanjie Niu, Amilcar Flores-Morales
• Journal: Molecular cancer (Mol Cancer) Vol. 14 Pg. 8 (Jan 27 2015) ISSN: 1476-4598 [Electronic] England
• PMID: 25623341 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Tumor Suppressor Protein p53
• Cysteine Endopeptidases
• rhoA GTP-Binding Protein

Topics

• Animals
• Carcinogenesis (metabolism)
• Cell Line
• Cell Line, Tumor
• Cell Proliferation (physiology)
• Cysteine Endopeptidases (metabolism)
• Humans
• Male
• Mice
• Mice, Nude
• Neoplasm Invasiveness (pathology)
• Prostatic Neoplasms (metabolism, pathology)
• Tumor Suppressor Protein p53 (metabolism)
• Ubiquitination (physiology)
• rhoA GTP-Binding Protein (metabolism)