PTB-associated splicing factor (PSF) is a PPARγ-binding protein and growth regulator of colon cancer cells

PLoS One. 2013;8(3):e58749. doi: 10.1371/journal.pone.0058749. Epub 2013 Mar 13.

Abstract

Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor that plays an essential role in cell proliferation, apoptosis, and inflammation. It is over-expressed in many types of cancer, including colon, stomach, breast, and lung cancer, suggesting that regulation of PPARγ might affect cancer pathogenesis. Here, using a proteomic approach, we identify PTB-associated splicing factor (PSF) as a novel PPARγ-interacting protein and demonstrate that PSF is involved in several important regulatory steps of colon cancer cell proliferation. To investigate the relationship between PSF and PPARγ in colon cancer, we evaluated the effects of PSF expression in DLD-1 and HT-29 colon cancer cell lines, which express low and high levels of PPARγ, respectively PSF affected the ability of PPARγ to bind, and expression of PSF siRNA significantly suppressed the proliferation of colon cancer cells. Furthermore, PSF knockdown induced apoptosis via activation of caspase-3. Interestingly, DLD-1 cells were more susceptible to PSF knockdown-induced cell death than HT-29 cells. Our data suggest that PSF is an important regulator of cell death that plays critical roles in the survival and growth of colon cancer cells. The PSF-PPARγ axis may play a role in the control of colorectal carcinogenesis. Taken together, this study is the first to describe the effects of PSF on cell proliferation, tumor growth, and cell signaling associated with PPARγ.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Proliferation
  • Colonic Neoplasms / pathology*
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • HT29 Cells
  • Humans
  • PPAR gamma / metabolism*
  • PTB-Associated Splicing Factor
  • Protein Binding
  • RNA, Small Interfering / genetics
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Vacuoles / metabolism

Substances

  • PPAR gamma
  • PTB-Associated Splicing Factor
  • RNA, Small Interfering
  • RNA-Binding Proteins

Grants and funding

This work was supported by Grants-in-Aid for Scientific Research (C) 22591482 (to Tamotsu Tsukahara) from the Japan Society for the Promotion of Science, and Grants-in-Aid from Takeda Science Foundation (to Tamotsu Tsukahara) and Astellas foundation for research on metabolic disorders (to Tamotsu Tsukahara). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.