| First Author | Li XM | Year | 2017 |
| Journal | PLoS One | Volume | 12 |
| Issue | 2 | Pages | e0171347 |
| PubMed ID | 28170411 | Mgi Jnum | J:251721 |
| Mgi Id | MGI:5926283 | Doi | 10.1371/journal.pone.0171347 |
| Citation | Li XM, et al. (2017) Nur77 deficiency in mice accelerates tumor invasion and metastasis by facilitating TNFalpha secretion and lowering CSF-1R expression. PLoS One 12(2):e0171347 |
| abstractText | Nur77, an orphan member of the nuclear receptor superfamily, plays critical roles in inflammation and immunity. However, the role of Nur77 in tumor microenvironment remains elusive. Results showed that deletion of Nur77 strikingly enhanced tumor metastasis compared to WT mice. Additionally, compared to the conditioned media derived from Nur77+/+ peritoneal macrophages (CM1), the conditioned media derived from Nur77-/- peritoneal macrophages (CM2) significantly promoted the EMT of cancer cells, and greatly enhanced the migratory and invasive abilities of cancer cells. Moreover, studies using TNF-alpha blocking antibody demonstrated that pro-inflammatory cytokine TNF-alpha was indispensable in supporting CM2-induced EMT to drive cancer cells migration and invasion. Furthermore, we found that Nur77 promoted the expression of CSF-1R, a novel downstream target gene of Nur77, and subsequently enhanced the migration of inflammatory cells. Notably, infiltration of inflammatory cells in the tumors of Nur77-/- mice was markedly abrogated compared to Nur77+/+ mice. Collectively, these results revealed that host Nur77 expression was pivotal in antitumor immune response, and in inhibiting tumor metastasis. |
