Interactome analysis reveals that C1QBP (complement component 1, q subcomponent binding protein) is associated with cancer cell chemotaxis and metastasis

Mol Cell Proteomics. 2013 Nov;12(11):3199-209. doi: 10.1074/mcp.M113.029413. Epub 2013 Aug 7.

Abstract

The complement component 1, q subcomponent binding protein (C1QBP/p32/HABP1) is a ubiquitously expressed and multicompartmental cellular protein involved in various biological processes. In order to further understand its biological functions, we conducted proteomics analysis of its interactome in this study. An improved sample preparation and mass spectrometric identification strategy was developed combining high-speed centrifugation, formaldehyde labeling, and two-dimensional reverse-phase liquid chromatography. Using this approach, we identified 187 interacting proteins and constructed a highly connected interacting network for C1QBP. Moreover, we explored the interaction between C1QBP and protein kinase C ζ, a key regulator of cell polarity and migration. The results indicated that C1QBP regulated the activity of protein kinase C ζ and modulated EGF-induced cancer cell chemotaxis. In addition, C1QBP was required for breast cancer metastasis in a severe combined immunodeficiency mouse model. Furthermore, C1QBP was observed to be overexpressed in breast cancer tissues, and its expression level was closely linked with distant metastasis and TNM stages. In summary, C1QBP was identified as a novel regulator of cancer metastasis that may serve as a therapeutic target for breast cancer treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Carcinoma, Ductal, Breast / genetics
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / secondary
  • Carrier Proteins / antagonists & inhibitors
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Membrane / metabolism
  • Chemotaxis / physiology
  • Chromatography, High Pressure Liquid
  • Female
  • Gene Knockdown Techniques
  • HEK293 Cells
  • Heterografts
  • Humans
  • Mice
  • Mice, SCID
  • Middle Aged
  • Mitochondrial Proteins / antagonists & inhibitors
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Neoplasm Metastasis / pathology
  • Neoplasm Metastasis / physiopathology
  • Protein Interaction Maps
  • Protein Kinase C / metabolism
  • Proteomics
  • Signal Transduction
  • Tandem Mass Spectrometry

Substances

  • C1QBP protein, human
  • Carrier Proteins
  • Mitochondrial Proteins
  • protein kinase C zeta
  • Protein Kinase C