Open AccessNur77 deficiency in mice accelerates tumor invasion and metastasis by facilitating TNFα secretion and lowering CSF-1R expression
Author(s) -
Xiu-Ming Li,
Jingru Wang,
Tong Shen,
Shasha Gao,
Xiaoshun He,
Jiangnan Li,
Tianyu Yang,
Shen Zhang,
Wen-Juan Gan,
Jianming Li,
Hua Wu
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0171347
Subject(s) - nerve growth factor ib , tumor necrosis factor alpha , cancer research , tumor microenvironment , cytokine , metastasis , biology , inflammation , cancer cell , immune system , microbiology and biotechnology , immunology , cancer , transcription factor , nuclear receptor , gene , biochemistry , genetics
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-α blocking antibody demonstrated that pro-inflammatory cytokine TNF-α 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.