HCRP-1 regulates cell migration and invasion via EGFR-ERK mediated up-regulation of MMP-2 with prognostic significance in human renal cell carcinoma

Sci Rep. 2015 Aug 25:5:13470. doi: 10.1038/srep13470.

Abstract

Previous studies indicated a role of hepatocellular carcinoma-related protein-1(HCRP-1) in human cancers, however, its expression pattern in renal cell carcinoma (RCC) and the molecular mechanism of HCRP-1 on cancer progression have not been characterized. In the present study, HCRP-1 expression was examined in a RCC tissue microarray. The negative expression of HCRP-1 was significantly correlated with tumor grade (P = 0.002), TNM stage (P = 0.001) and pT status (P = 0.003). Furthermore, we showed a strong correlation between negative HCRP-1 expression and worse overall and disease-specific survival (P = 0.0003 and P = 0.0012, respectively). Knockdown of HCRP-1 promoted cell migration and invasion in 786-O and OS-RC-2 cell lines. HCRP-1 depletion increased matrix metalloproteinase (MMP)-2 protein level, with increased extracellular signal-regulatedkinase (ERK) phosphorylation, which could be reversed by ERK siRNA or ERK inhibitor, PD98059. Further analysis showed that HCRP-1 knockdown induced epidermal growth factor receptor (EGFR) phosphorylation. Treatment with EGFR inhibitor or EGFR siRNA blocked HCRP-1-mediated up-regulation of EGFR, ERK phosphorylation and MMP-2 expression. In summary, our results showed that negative HCRP-1 expression is an independent prognostic factor for RCC patients and promotes migration and invasion by EGFR-ERK-mediated up-regulation of MMP-2. HCRP-1 may serve as a therapeutic target for RCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Carcinoma, Renal Cell / metabolism*
  • Carcinoma, Renal Cell / mortality*
  • Carcinoma, Renal Cell / pathology
  • Cell Line, Tumor
  • Cell Movement
  • China / epidemiology
  • Endosomal Sorting Complexes Required for Transport / metabolism*
  • ErbB Receptors / metabolism
  • Humans
  • Incidence
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / mortality*
  • Kidney Neoplasms / pathology
  • MAP Kinase Signaling System
  • Matrix Metalloproteinase 2 / metabolism*
  • Neoplasm Invasiveness
  • Prognosis
  • Reproducibility of Results
  • Risk Factors
  • Sensitivity and Specificity
  • Signal Transduction
  • Survival Rate
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • Endosomal Sorting Complexes Required for Transport
  • VPS37A protein, human
  • EGFR protein, human
  • ErbB Receptors
  • MMP2 protein, human
  • Matrix Metalloproteinase 2