Involvement of the prostaglandin D2 signal pathway in retinoid-inducible gene 1 (RIG1)-mediated suppression of cell invasion in testis cancer cells

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• 作者：Chang-Chieh Wu^a ; Rong-Yaun Shyu^b ; Chun-Hua Wang^c ; Tzung-Chieh Tsai^d ; Lu-Kai Wang^e ; Mao-Liang Chen^f ; Shun-Yuan Jiang^f ; Fu-Ming Tsai^f ; ^{afu2215@gmail.com}
• 关键词：Retinoid-inducible gene 1 ; Prostaglandin D2 synthase ; Testis ; HREV107 type II tumor suppressor
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular Cell Research
• 出版年：2012
• 出版时间：December, 2012
• 年：2012
• 卷：1823
• 期：12
• 页码：2227-2236
• 全文大小：1359 K

文摘

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.