GOLPH3 is a potential therapeutic target and a prognostic indicator of poor survival in bladder cancer treated by cystectomy

Qing Zhang; Junlong Zhuang; Yongming Deng; Xiaozhi Zhao; Bo Tang; Dongwei Yao; Wei Zhao; Cunjie Chang; Qun Lu; Wei Chen; Shiwei Zhang; Changwei Ji; Lin Cao; Hongqian Guo

doi:10.18632/oncotarget.4867

GOLPH3 is a potential therapeutic target and a prognostic indicator of poor survival in bladder cancer treated by cystectomy

Oncotarget. 2015 Oct 13;6(31):32177-92. doi: 10.18632/oncotarget.4867.

Authors

Qing Zhang¹, Junlong Zhuang¹, Yongming Deng¹, Xiaozhi Zhao¹, Bo Tang², Dongwei Yao¹, Wei Zhao³, Cunjie Chang³, Qun Lu¹, Wei Chen¹, Shiwei Zhang¹, Changwei Ji¹, Lin Cao^{4

2}, Hongqian Guo¹

Affiliations

¹ Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University, Nanjing 210008, Jiangsu, PR China.
² Vazyme Biotech Co., Ltd, Nanjing 210000, Jiangsu, PR China.
³ MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, Jiangsu 210061, China.
⁴ College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210095, Jiangsu, PR China.

Abstract

Golgi phosphoprotein 3 (GOLPH3) has been reported to be involved in the development of several human cancers. However, its clinical significance and biological role in bladder cancer remains unclear. In this study, we sought to analyze the GOLPH3 expression in bladder cancer samples and cells, and explore its clinical significance and biological role. We found that GOLPH3 was significantly increased in bladder cancer tissues and cells. Overexpression of GOLPH3 had significant correlation with poorer survival for bladder cancer patients treated by cystectomy. Knockdown of GOLPH3 inhibited the proliferation, migration and invasion of cancer cells, and tumor growth in a xenograft mouse model. GOLPH3 silencing inhibited AKT/m-TOR signaling, increased the cyclin-dependent kinase (CDK) inhibitor p27 and decreased the CDK regulator cyclin D1 and matrix metallopeptidase 9 (MMP9). Thus, GOLPH3 is likely to play important roles in bladder cancer progression via modulating AKT/mTOR signaling, and it is a novel prognostic biomarker and promising therapeutic target for bladder cancer.

Keywords: AKT/mTOR signalling; GOLPH3; bladder cancer; prognosis; survival.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Animals
Biomarkers, Tumor / genetics
Biomarkers, Tumor / metabolism*
Cell Line, Tumor
Cell Movement
Cell Proliferation
Cyclin-Dependent Kinase Inhibitor p27 / metabolism
Cystectomy* / adverse effects
Cystectomy* / mortality
Female
Gene Expression Regulation, Neoplastic
Humans
Kaplan-Meier Estimate
Male
Matrix Metalloproteinase 9 / metabolism
Membrane Proteins / genetics
Membrane Proteins / metabolism*
Mice, Inbred BALB C
Mice, Nude
Middle Aged
Neoplasm Invasiveness
Proto-Oncogene Proteins c-akt / metabolism
RNA Interference
Retrospective Studies
Risk Factors
Signal Transduction
TOR Serine-Threonine Kinases / metabolism
Time Factors
Transfection
Treatment Outcome
Up-Regulation
Urinary Bladder Neoplasms / genetics
Urinary Bladder Neoplasms / metabolism*
Urinary Bladder Neoplasms / mortality
Urinary Bladder Neoplasms / pathology
Urinary Bladder Neoplasms / surgery*

Substances

Biomarkers, Tumor
CDKN1B protein, human
GOLPH3 protein, human
Membrane Proteins
Cyclin-Dependent Kinase Inhibitor p27
MTOR protein, human
Proto-Oncogene Proteins c-akt
TOR Serine-Threonine Kinases
MMP9 protein, human
Matrix Metalloproteinase 9