Fibrinogen‑like‑protein 1 promotes the invasion and metastasis of gastric cancer and is associated with poor prognosis

Abstract

The protective role of fibrinogen-like-protein 1 (FGL1) in liver injury has been reported previously. However, there are few studies on FGL1 expression in gastric cancer (GC) tissues, and the role of FGL1 in GC remains unclear. The aim of the present study was to investigate the correlation between FGL1 expression and prognosis in GC patients. Data was downloaded from The Cancer Genome Atlas database, and 50 pairs of GC tissues and the corresponding non-tumor tissues were collected between 2008 to 2011. Furthermore, FGL1 expression was silenced in order to explore its role in SGC-7901 cell proliferation, invasion and migration using Cell Counting Kit-8, wound healing, Transwell invasion and migration assays, respectively. Finally, whether FGL1 is involved in epithelial-mesenchymal transition (EMT) regulation in SGC-7901 cells was determined by western blotting. The results revealed that FGL1 expression was upregulated in GC tissues, and the overall survival time of GC patients with high FGL1 expression levels was markedly shorter than that of GC patients with low FGL1 expression levels (P=0.005). In addition, silencing FGL1 significantly inhibited SGC-7901 cell proliferation, invasion and migration in vitro. Finally, western blot analyses indicated that knockdown of FGL1 markedly increased E-cadherin expression levels (P<0.01), and significantly decreased N-cadherin (P<0.01) and vimentin expression levels (P<0.01), thereby suggesting that FGL1 may promote EMT. These results indicated that FGL1 has the potential to be a predictor in GC patients as well as a target for the treatment of GC.

FGL1 Regulates Acquired Resistance to Gefitinib by Inhibiting Apoptosis in Non-small Cell Lung Cancer

“…Several recent studies have shown that FGL1 is signi cantly upregulated in NSCLC patients and is closely correlated to the poor prognosis of these patients [7,31,34,36]. Further, FGL1 may be an important factor involved in epithelial-mesenchymal transition by in uencing cell-cell adhesion and information transmission [37,38]. Our previous study also revealed that loss of FGL1 did not induce but inhibited epithelial-mesenchymal transition in PC9/GR cells [39].…”

“…It has also been shown that STAT3 signaling is involved in the regeneration and apoptosis of liver injury [33,41,42], and phosphorylated STAT3 regulated the expression of Bax, Bcl-2, and cell cycle-regulatory genes (including c-fos, c-myc, and cyclin), indicating its role in cell proliferation and apoptosis [43]. Although overexpression of FGL1 has been con rmed in several tumors and contributes to poor prognosis [31,[36][37][38]40], FGL1 expression is downregulated in HCC, and loss of FGL1 may lead to the low differentiation of HCC cells [31,36,40]. This difference may be closely related to the differentiation of tumor cells [40] and their surrounding microenvironment [28,38].…”

“…Although overexpression of FGL1 has been con rmed in several tumors and contributes to poor prognosis [31,[36][37][38]40], FGL1 expression is downregulated in HCC, and loss of FGL1 may lead to the low differentiation of HCC cells [31,36,40]. This difference may be closely related to the differentiation of tumor cells [40] and their surrounding microenvironment [28,38]. In the current study, we found that knockdown of FGL1 led to clearly enhanced the expression of cleaved caspase 3 and cleaved PARP1, and overcame acquired resistance to ge tinib in NSCLC cells both in vitro and in vivo.…”

Systematic Development of Sandwich Immunoassays for the Plasma Secretome

“…Plasma levels of NPPA have been described as prognostic predictors in patients with chronic heart failure, but are also known to reflect the severity of left ventricular hemodynamic dysfunction [15]. It has been suggested that FGL1 plays a role in liver protection and liver regeneration, but it also has the potential to serve as a target for the treatment of gastric cancer and to predict gastric cancer prognosis [16]. In addition, CCL16, a human CC chemokine, has been shown to be differentially expressed in ovarian cancer [17,18].…”

Immunological Targets for Immunotherapy: Inhibitory T Cell Receptors

“…FGL1 belongs to the fibrinogen family of proteins which includes fibrinogen, FGL-1, FGL-2 and clotting factors V, VIII and XIII. FGL-1 is predominantly expressed by the liver, and by human cancers including gastric cancer [153] where it is associated with poor prognosis. FGL-1's fibrinogen-like domain interacts with LAG-3 either at membrane-distal D1 or D2 domains, although the specific means by which the FGL-1-LAG-3 interaction inhibits antigen-specific T cell activation remain unclear.…”