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.

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