Emerging role of CCN family proteins in tumorigenesis and cancer metastasis (Review)

Int J Mol Med. 2015 Dec;36(6):1451-63. doi: 10.3892/ijmm.2015.2390. Epub 2015 Oct 23.


The CCN family of proteins comprises the members CCN1, CCN2, CCN3, CCN4, CCN5 and CCN6. They share four evolutionarily conserved functional domains, and usually interact with various cytokines to elicit different biological functions including cell proliferation, adhesion, invasion, migration, embryonic development, angiogenesis, wound healing, fibrosis and inflammation through a variety of signalling pathways. In the past two decades, emerging functions for the CCN proteins (CCNs) have been identified in various types of cancer. Perturbed expression of CCNs has been observed in a variety of malignancies. The aberrant expression of certain CCNs is associated with disease progression and poor prognosis. Insight into the detailed mechanisms involved in CCN-mediated regulation may be useful in understanding their roles and functions in tumorigenesis and cancer metastasis. In this review, we briefly introduced the functions of CCNs, especially in cancer.

Publication types

  • Review

MeSH terms

  • CCN Intercellular Signaling Proteins / genetics*
  • CCN Intercellular Signaling Proteins / metabolism
  • Carcinogenesis / genetics
  • Carcinogenesis / metabolism
  • Connective Tissue Growth Factor / genetics*
  • Connective Tissue Growth Factor / metabolism
  • Cysteine-Rich Protein 61 / genetics*
  • Cysteine-Rich Protein 61 / metabolism
  • Humans
  • Neoplasm Metastasis
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Nephroblastoma Overexpressed Protein / genetics*
  • Nephroblastoma Overexpressed Protein / metabolism
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism


  • CCN Intercellular Signaling Proteins
  • CCN1 protein, human
  • CCN2 protein, human
  • CCN3 protein, human
  • CCN4 protein, human
  • CCN5 protein, human
  • CCN6 protein, human
  • Cysteine-Rich Protein 61
  • Nephroblastoma Overexpressed Protein
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • Connective Tissue Growth Factor