がんの科学と治療

New Insights into the PTB-Associated Splicing Factor (PSF) and Peroxisome Proliferator Activated Receptor gamma (PPARγ) in Colorectal Carcinogenesis

Abstract

Tamotsu Tsukahara, Yoshikazu Matsuda and Hisao Haniu

PTB-associated Splicing Factor (PSF) is a multifunctional protein involved in transcription repression, premRNA processing, and DNA repair. Transcriptional repression by PSF is mediated by its interaction with nuclear hormone receptors. However, the physiological context of PSF in regard to nuclear receptor signaling is still unclear. In this review, our recent study identified PSF as a novel PPARγ-interacting protein and demonstrated that PSF is involved in several important regulatory steps of colon cancer cell proliferation. Recently, the aberrant expression of PSF in tumor cells has been implicated in resistance to drugs that are commonly used in cancer therapy. Therefore, it might be possible to develop and to optimize drugs that inhibit PSF and correct abnormal splicing, resulting in enhanced tumor cell migration, invasion, and proliferation. In this review, we summarize current understanding of the mechanisms underlying the PSF-PPARγ axis and its role in the control of colorectal carcinogenesis.