Elevated S100A6 (Calcyclin) enhances tumorigenesis and suppresses CXCL14-induced apoptosis in clear cell renal cell carcinoma

Oncotarget. 2015 Mar 30;6(9):6656-69. doi: 10.18632/oncotarget.3169.

Abstract

Clear cell renal cell carcinoma (ccRCC) is often resistant to existing therapy. We found elevated S100A6 levels in ccRCC tissues, associated with higher grade pathological features and clinical stages in ccRCC patients. Knockdown of S100A6 inhibited cell proliferation in vitro and tumor growth in vivo. Gene expression profiling suggests a novel function of S100A6 in suppressing apoptosis, as well as a relationship between S100A6 and CXCL14, a pro-inflammatory chemokine. We suggest that the S100A6/CXCL14 signaling pathway is a potential therapeutic target in ccRCC.

Keywords: CXCL14; S100A6; apoptosis; clear cell renal cell carcinoma; tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Apoptosis*
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / metabolism*
  • Carcinoma, Renal Cell / pathology
  • Cell Cycle Checkpoints
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation
  • Chemokines, CXC / genetics
  • Chemokines, CXC / metabolism*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Gene Regulatory Networks
  • Humans
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / pathology
  • Male
  • Mice, Inbred NOD
  • Mice, SCID
  • Middle Aged
  • Neoplasm Grading
  • RNA Interference
  • S100 Calcium Binding Protein A6
  • S100 Proteins / genetics
  • S100 Proteins / metabolism*
  • Signal Transduction
  • Time Factors
  • Transfection
  • Tumor Burden
  • Up-Regulation

Substances

  • CXCL14 protein, human
  • Cell Cycle Proteins
  • Chemokines, CXC
  • S100 Calcium Binding Protein A6
  • S100 Proteins
  • S100A6 protein, human