title: Involvement of the prostaglandin D2 signal pathway in retinoid-inducible gene 1 (RIG1)-mediated suppression of cell invasion in testis cancer cells.
abstract: Retinoid-inducible gene 1 (RIG1), also called tazarotene-induced gene 3, belongs to the HREV107 gene family, which contains five members in humans. RIG1 is expressed in high levels in well-differentiated tissues, but its expression is decreased in cancer tissues and cancer cell lines. We found RIG1 to be highly expressed in testicular cells. When RIG1 was expressed in NT2/D1 testicular cancer cells, neither cell death nor cell viability was affected. However, RIG1 significantly inhibited cell migration and invasion in NT2/D1 cells. We found that prostaglandin D2 synthase (PTGDS) interacted with RIG1 using yeast two-hybrid screens. Further, we found PTGDS to be co-localized with RIG1 in NT2/D1 testis cells. In RIG1-expressing cells, elevated levels of prostaglandin D2 (PGD2), cAMP, and SRY-related high-mobility group box 9 (SOX9) were observed. This indicated that RIG1 can enhance PTGDS activity. Silencing of PTGDS expression significantly decreased RIG1-mediated cAMP and PGD2 production. Furthermore, silencing of PTGDS or SOX9 alleviated RIG1-mediated suppression of migration and invasion. These results suggest that RIG1 will suppress cell migration/invasion through the PGD2 signaling pathway. In conclusion, RIG1 can interact with PTGDS to enhance its function and to further suppress NT2/D1 cell migration and invasion. Our study suggests that RIG1-PGD2 signaling might play an important role in cancer cell suppression in the testis.
authors.affiliation: Department of Surgery, Tri-Service General Hospital, Taipei 114, Taiwan.
authors.forename: Chang-Chieh
authors.initials: CC
authors.lastname: Wu
authors.forename: Rong-Yaun
authors.initials: RY
authors.lastname: Shyu
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Wang
authors.forename: Tzung-Chieh
authors.initials: TC
authors.lastname: Tsai
authors.forename: Lu-Kai
authors.initials: LK
authors.lastname: Wang
authors.forename: Mao-Liang
authors.initials: ML
authors.lastname: Chen
authors.forename: Shun-Yuan
authors.initials: SY
authors.lastname: Jiang
authors.forename: Fu-Ming
authors.initials: FM
authors.lastname: Tsai
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D000242:Cyclic AMP / Q000378:metabolism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D047468:Immunoprecipitation; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D054834:Lipocalins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009361:Neoplasm Invasiveness; D015230:Prostaglandin D2 / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011982:Receptors, Prostaglandin / Q000235:genetics / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013736:Testicular Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D013737:Testis / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D054834:Lipocalins; C437968:PLAAT4 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011982:Receptors, Prostaglandin; D018168:Receptors, Retinoic Acid; D000242:Cyclic AMP; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D015230:Prostaglandin D2