DCN deficiency promotes renal cell carcinoma growth and metastasis through downregulation of P21 and E-cadherin

Tumour Biol. 2016 Apr;37(4):5171-83. doi: 10.1007/s13277-015-4160-1. Epub 2015 Nov 7.

Abstract

Decorin (DCN), as an important component of the extracellular matrix (ECM), is a small leucine-rich proteoglycan and synthesized by fibroblasts. Although DCN is dysregulated in numerous cancer types, limited data are available on the expression level and important role of DCN proteins in renal cell carcinoma (RCC). In our study, we examined the expression patterns of DCN messenger RNA (mRNA) in RCCs through the Oncomine database and DCN protein in 94 RCC specimens by immunohistochemistry (IHC). The results revealed that DCN expression was decreased in cancerous tissues compared to adjacent noncancerous tissues and was highly correlated to tumor size. Then, via gain-of-function analyses, DCN overexpression could inhibit RCC cell proliferation and metastasis in vitro and vivo. At the mechanism level, we found that an ectopic expression of DCN significantly upregulated P21 and E-cadherin expression. Altogether, these results revealed that DCN is a tumor suppressor in RCC, and it could serve as a potential therapeutic target in patients with RCC.

Keywords: DCN protein; Metastasis; Molecular mechanism; Proliferation; Renal cell carcinoma.

MeSH terms

  • Aged
  • Animals
  • Cadherins / biosynthesis*
  • Cadherins / genetics
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / biosynthesis*
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Decorin / biosynthesis*
  • Decorin / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Middle Aged
  • Neoplasm Metastasis
  • RNA, Messenger / biosynthesis
  • Xenograft Model Antitumor Assays

Substances

  • CDKN1A protein, human
  • Cadherins
  • Cyclin-Dependent Kinase Inhibitor p21
  • DCN protein, human
  • Decorin
  • RNA, Messenger