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.