Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P05412 (
c-Jun
)
11,453
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
M2-polarized (alternatively activated) macrophages play an important role in the progression of hepatocellular carcinoma (HCC).
Allograft inflammatory factor 1
(
AIF1
) is overexpressed in M2-polarized macrophages. This study explored the role of
AIF1
in tumor-associated macrophages in HCC. Macrophages were stimulated with colony-stimulating factor 1 (CSF1) to characterize the regulatory pathway of
AIF1
in macrophages. The chromatin immunoprecipitation and luciferase reporter gene assay were conducted to examine transcription factors associated with
AIF1
expression.
AIF1
was down or upregulated, and the effects on tumor progression were evaluated by using
in vitro
and
in vivo
co-culture systems. A cytokine array was performed to screen the downstream functional components of
AIF1
. Tumor tissue from 206 patients with HCC were used to explore the clinical significance of
AIF1
.
AIF1
induced a M2-like phenotype of macrophages. By facilitating the binding of
c-Jun
to the promoter of
AIF1
, CSF1 secreted from hepatoma cells increased
AIF1
expression through the CSF1R-MEK1/2-Erk1/2-
c-Jun
axis.
AIF1
expressed in macrophages promoted the migration of hepatoma cells in co-culture system of RAW264.7 and Hepa1-6 and tumor growth in an animal model. The cytokine array showed that CXCL16 was increased in RAW264.7 cells with overexpressed
AIF1
, leading to enhanced tumor cell migration. In human HCC tissue,
AIF1
-positive macrophages in the adjacent microenvironment was associated with microvascular invasion and advanced TNM stages and with patients' overall and disease-free survival (
p
= 0.002 for both).
AIF1
expression in macrophages plays a pivotal role in the interaction between macrophages and hepatoma cells.
...
PMID:Colony-stimulating factor-1-induced AIF1 expression in tumor-associated macrophages enhances the progression of hepatocellular carcinoma. 2893 35
