H-rev107 regulates prostaglandin D2 synthase-mediated suppression of cellular invasion in testicular cancer cells

Rong-Yaun Shyu,Lu-Kai Wang,Mao-Liang Chen,Shun-Yuan Jiang,Tzung-Chieh Tsai,Chang-Chieh Wu,Fu-Ming Tsai,Chun-Hua Wang

doi:10.1186/1423-0127-20-30

Abstract

BackgroundH-rev107 is a member of the HREV107 type II tumor suppressor gene family which includes H-REV107, RIG1, and HRASLS. H-REV107 has been shown to express at high levels in differentiated tissues of post-meiotic testicular germ cells. Prostaglandin D2 (PGD2) is conjectured to induce SRY-related high-mobility group box 9 (SOX9) expression and subsequent Sertoli cell differentiation. To date, the function of H-rev107 in differentiated testicular cells has not been well defined.ResultsIn the study, we found that H-rev107 was co-localized with prostaglandin D2 synthase (PTGDS) and enhanced the activity of PTGDS, resulting in increase of PGD2 production in testis cells. Furthermore, when H-rev107 was expressed in human NT2/D1 testicular cancer cells, cell migration and invasion were inhibited. Also, silencing of PTGDS would reduce H-rev107-mediated increase in PGD2, cAMP, and SOX9. Silencing of PTGDS or SOX9 also alleviated H-rev107-mediated suppression of cell migration and invasion.ConclusionsThese results revealed that H-rev107, through PTGDS, suppressed cell migration and invasion. Our data suggest that the PGD2-cAMP-SOX9 signal pathway might play an important role in H-rev107-mediated cancer cell invasion in testes.

Highlights

H-rev107 is a member of the HREV107 type II tumor suppressor gene family which includes H-REV107, retinoidinducible gene 1 (RIG1), and HRASLS
RIG1 has been shown to stimulate cellular differentiation which is mediated by activating type I tissue transglutaminase [13,23]. These results suggest that RIG1, HRASLS2, and H-REV107 can regulate cellular differentiation in various tissues through different downstream signal pathways
The expression of H-rev107 and prostaglandin D2 synthase (PTGDS) was confirmed by Western blotting in testis cell extracts prepared from three mice (Figure 1B)

Summary

Introduction

H-rev107 is a member of the HREV107 type II tumor suppressor gene family which includes H-REV107, RIG1, and HRASLS. H-rev107 [1], called HRASLS3 [2] or PLA2G16 [3], is a member of the HREV107 type II tumor suppressor gene family, which includes H-REV107, retinoidinducible gene 1 (RIG1) [4], HRASLS2 [5,6], HRLP5 [7], and HRASLS [8] The protein in this family contains an NC domain, with unknown function at the N-terminus, and a hydrophobic membrane-anchoring domain at the C-terminus [9,10]. H-REV107 is expressed at high levels in differentiated tissues of post-meiotic testicular germ cells but not in testicular germ cell tumors [17] Both genes are expressed in normal tissues in a tissue-specific manner and are downregulated in various cancer tissues [15,16,17,18]. The HREV107 protein family might play an important role in the regulation of cell growth and differentiation in both normal and cancer cells

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Conclusion