Pyk2 and Src mediate signaling to CCL18-induced breast cancer metastasis

J Cell Biochem. 2014 Mar;115(3):596-603. doi: 10.1002/jcb.24697.

Abstract

Pyk2 and Src phosphorylation is initiated by CCL18, which promotes breast cancer metastasis via its functional G protein-coupled receptor PITPNM3. However, the function of Pyk2 and Src in CCL18-induced breast cancer metastasis is poorly understood. Quantitative reverse-transcription polymerase chain reactions (qRT-PCRs), Western blot, boyden chamber assay, and adherence assay were performed to delineate the consequences of Pyk2/Src in CCL18-induced breast cancer cells. Co-immunoprecipitation and immunofluorescence were performed to analyze the interaction of proteins. Upon the binding of CCL18 to PITPNM3, Pyk2 translocates from the cytoplasm to the plasma membrane to form a stable complex with PITPNM3, subsequently activating Src kinase. Moreover, upon stimulation with CCL18, Pyk2 and Src become essential for integrin alpha5/beta1 clustering-dependent adherence, migration, and invasion. Pyk2 and Src are important in CCL18-induced breast cancer metastasis.

Keywords: CCL18; INTEGRIN; METASTASIS; Pyk2; Src.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Calcium-Binding Proteins / metabolism
  • Cell Line, Tumor
  • Chemokines, CC / genetics*
  • Female
  • Focal Adhesion Kinase 2 / genetics
  • Focal Adhesion Kinase 2 / metabolism*
  • Humans
  • Membrane Proteins / metabolism
  • Neoplasm Metastasis
  • src-Family Kinases / genetics
  • src-Family Kinases / metabolism*

Substances

  • CCL18 protein, human
  • Calcium-Binding Proteins
  • Chemokines, CC
  • Membrane Proteins
  • PITPNM3 protein, human
  • Focal Adhesion Kinase 2
  • src-Family Kinases