Showing papers on "Friend leukemia published in 2019"
TL;DR: A combined role for FLI1 as a suppressor of invasiveness and proliferation in gastric adenocarcinoma, specifically in the transition from pre-cancer lesions and dysplasia to invasive adenOCarcinomas is supported, and it is suggested thatFLI1 may be a prognostic biomarker of survival in Gastric cancers.
Abstract: Gastric adenocarcinoma (GC) is a leading cause of cancer-related deaths worldwide. The transcription factor gene Friend Leukemia Integration 1 (FLI1) is methylated and downregulated in human GC tissues. Using human GC samples, we determined which cells downregulate FLI1, when FLI1 downregulation occurs, if FLI1 downregulation correlates with clinical-pathologic characteristics, and whether FLI1 plays a role in invasion and/or proliferation of cultured cells. We analyzed stomach tissues from 98 patients [8 normal mucosa, 8 intestinal metaplasia (IM), 7 dysplasia, 91 GC] by immunohistochemistry for FLI1. Epithelial cells from normal, IM, and low-grade dysplasia (LGD) showed strong nuclear FLI1 staining. GC epithelial cells showed significantly less nuclear FLI1 staining as compared to normal epithelium, IM and LGD (P=1.2×10-5, P=1.4×10-6 and P=0.006, respectively). FLI1 expression did not correlate with tumor stage or differentiation, but was associated with patient survival, depending on tumor differentiation. We tested the functional role of FLI1 by assaying proliferation and invasion in cultured GC cells. Lentiviral-transduced FLI1 overexpression in GC AGS cells inhibited invasion by 73.5% (P = 0.001) and proliferation by 31.5% (P = 0.002), as compared to controls. Our results support a combined role for FLI1 as a suppressor of invasiveness and proliferation in gastric adenocarcinoma, specifically in the transition from pre-cancer lesions and dysplasia to invasive adenocarcinoma, and suggest that FLI1 may be a prognostic biomarker of survival in gastric cancers.
4 citations
26 Jun 2019
TL;DR: It is hypothesize that targeting the regulation of ERG, FLI-1 and ERG-mediation of TGF-β1/Smad3 signaling may be a promising therapeutic strategy in PAH and IPF.
Abstract: Pulmonary arterial hypertension (PAH) is a chronic debilitating cardiopulmonary disease characterized by abnormal remodeling of peripheral lung vasculature resulting in progressive vasoconstriction. Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and irreversible disease that is often associated with significant morbidity and poor quality of life. The prognosis of PAH and IPF is poor and currently available medications focus on relieving symptoms and slowing down progression. Hence, there is a clear necessity to develop new therapies. ETS-related genes and Friend leukemia integration–1 (FLI–1) are transcription factors involved in angiogenesis, cellular homeostasis, vascular remodeling, and the genetic regulation of inflammation, apoptosis, and fibrosis seen in PAH and IPF. Simultaneous small-interfering-RNA (siRNA) knockdown of ERG and FLI1 in human pulmonary artery endothelial cells (HPAEC) and human pulmonary microvasculature endothelial cells (HPMEC) has been associated with up-regulation of pro-inflammatory genes and interferon (IFN) pathway-related genes. Notably, the endothelium in normal lungs has also been shown to have high levels of nuclear ERG and Fli-1 compared to significantly lower levels in diseased lungs. Recently, ERG upregulation was found to promote liver homoeostasis by regulating canonical TGFβ1SMAD signaling and promoting the SMAD1 pathway while repressing SMAD3 activity. Improvement in pulmonary fibrosis through medications that suppress the TGF-β1/Smad3 pathway has also been a subject of study. In this review, we hypothesize that targeting the regulation of ERG, FLI-1 and ERG-mediation of TGF-β1/Smad3 signaling may be a promising therapeutic strategy in PAH and IPF. Keyword: Pulmonary Diseases, ETS genes, Signaling pathways, Targeted therapy, small molecules, Smad3 inhibitors, ERG/Fli-1 inducers.