PZR promotes metastasis of colorectal cancer through increasing FAK and Src phosphorylation

Acta Biochim Biophys Sin (Shanghai). 2019 Apr 1;51(4):356-364. doi: 10.1093/abbs/gmz019.

Abstract

Metastasis is the main cause of death in patients with colorectal cancer (CRC), but the molecular mechanism is not yet fully understood. Previous studies have shown that P zero-related protein (PZR), a member of the immunoglobulin family, can promote fibronectin-dependent migration of mouse embryonic fibroblasts as well as invasion and metastasis of hepatic carcinoma cells. However, the role of PZR in CRC remains unclear. In this study, we determined the ectopic expression of PZR in CRC tissues, and results showed that PZR expression was increased not only in tumors with higher pathological stage, but also in tumors with distant metastasis. Through PZR-knockdown and overexpression in CRC cell lines, we found that the expression of PZR had significant effect on the invasion and migration of CRC cells as well as the phosphorylation of pro-metastasis proteins including focal adhesion kinase (FAK) and Src. Taken together, this study indicates that PZR may promote the invasion and migration of CRC cells through increasing the phosphorylation of FAK and Src, which provides a new theoretical basis and a possible marker for the diagnosis or prognosis of CRC metastasis.

Keywords: FAK; PZR; Src; colorectal cancer; metastasis.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Focal Adhesion Protein-Tyrosine Kinases / genetics
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism*
  • HCT116 Cells
  • HEK293 Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Neoplasm Metastasis
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Prognosis
  • RNA Interference
  • src-Family Kinases / genetics
  • src-Family Kinases / metabolism*

Substances

  • Biomarkers, Tumor
  • Intracellular Signaling Peptides and Proteins
  • MPZL1 protein, human
  • Phosphoproteins
  • Focal Adhesion Protein-Tyrosine Kinases
  • src-Family Kinases