Involvement of the prostaglandin D2 signal pathway in retinoid-inducible gene 1 (RIG1)-mediated suppression of cell invasion in testis cancer cells.
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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DOI：
10.1016/j.bbamcr.2012.08.013
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发表时间：
2012-12
期刊：
影响因子：
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通讯作者：
Chang-Chieh Wu;R. Shyu;Chun-Hua Wang;T. Tsai;Lu-Kai Wang;Mao-Liang Chen;Shun-yuan Jiang;F. Tsai
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文献类型：
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作者：
Chang-Chieh Wu;R. Shyu;Chun-Hua Wang;T. Tsai;Lu-Kai Wang;Mao-Liang Chen;Shun-yuan Jiang;F. Tsai
类维生素A诱导基因1（RIG 1），也称为他扎罗汀诱导基因3，属于HREV 107基因家族，在人类中包含5个成员。RIG 1在分化良好的组织中以高水平表达，但其表达在癌组织和癌细胞系中降低。我们发现RIG 1在睾丸细胞中高度表达。当RIG 1在NT 2/D1睾丸癌细胞中表达时，细胞死亡和细胞活力均不受影响。然而，RIG 1显著抑制NT 2/D1细胞的细胞迁移和侵袭。我们发现，前列腺素D2合酶（PTGDS）与RIG 1相互作用，使用酵母双杂交筛选。此外，我们发现PTGDS与RIG 1在NT 2/D1睾丸细胞中共定位。在RIG 1表达细胞中，观察到前列腺素D2（PGD 2）、cAMP和SRY相关高迁移率族蛋白9（SOX 9）水平升高。这表明RIG 1可以增强PTGDS活性。PTGDS表达的沉默显著降低了RIG 1介导的cAMP和PGD 2的产生。此外，PTGDS或SOX 9的沉默减轻了RIG 1介导的对迁移和侵袭的抑制。这些结果表明，RIG 1将通过PGD 2信号通路抑制细胞迁移/侵袭。总之，RIG 1可以与PTGDS相互作用，以增强其功能，并进一步抑制NT 2/D1细胞的迁移和侵袭。我们的研究表明，RIG 1-PGD 2信号可能在睾丸癌细胞抑制中发挥重要作用。
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.