STEAP4 regulates focal adhesion kinase activation and CpG motifs within STEAP4 promoter region are frequently methylated in DU145, human androgen-independent prostate cancer cells.
The possible roles of STEAP4 in cancer progression have not been reported. In this study, we report that STEAP4 expression is able to inhibit anchorage-independent cell growth. We also demonstrate that STEAP4 associates with focal adhesion kinase (FAK) and regulate the activity of FAK through Y397 phosphorylation. Furthermore, we show that CpG sequences in STEAP4 promoter region were frequently methylated in DU145, androgen-independent prostate cancer cells. Demethylation treatment induced STEAP4 expression in DU145, suggesting the possibility that STEAP4 expression in cancer cells is in part epigenetically regulated. Collectively, these data demonstrate a novel function of STEAP4 and that STEAP4 may play an important role in tumor malignancy.
Tamura
Takahiko
T
Department of Biological Science and Technology, Tokyo University of Science, 2641 Yamazaki, Chiba 278-8510, Japan. tktamura@rs.noda.tus.ac.jp
Chiba
Joe
J
D000728:Androgens / Q000378:metabolism; D045744:Cell Line, Tumor; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D015536:Down-Regulation / Q000235:genetics; D004789:Enzyme Activation; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D011485:Protein Binding; D014410:Tumor Stem Cell Assay
D000728:Androgens; D008565:Membrane Proteins; D019000:Phosphotyrosine; D010088:Oxidoreductases; C503310:STEAP4 protein, human; D051416:Focal Adhesion Protein-Tyrosine Kinases