Interferon-inducible protein IFIXα inhibits cell invasion by upregulating the metastasis suppressor maspin

IFIXα, a member of the interferon-inducible HIN-200 family, has been identified as a putative tumor suppressor. However, the molecular mechanisms underlying IFIXα-mediated tumor suppression are poorly understood. In the present study, we demonstrated that the metastasis suppressor maspin acts as the downstream target of IFIXα. IFIXα suppressed the invasion activity of MDA-MB-468 breast cancer cells, and its inhibitory effect was reversed by the knockdown of maspin. Both Maspin mRNA and protein were upregulated by IFIXα. Histone deacetylase (HDAC) inhibitors, but not DNA methyltransferase inhibitor upregulated maspin, and HDAC1 inhibited the transactivation of maspin promoter. Although the HDAC1 protein was downregulated in IFIXα-expressing cells, IFIXα did not affect HDAC1 mRNA levels. Conversely, a proteasome inhibitor restored the level of HDAC1 protein in IFIXα-expressing cells, and the polyubiqutination of HDAC1 was promoted by IFIXα, suggesting that HDAC1 is regulated by IFIXα through a ubiquitin-proteasome pathway. Together, these data provide novel insights into the tumor-suppressive function of IFIXα.