The role of Fibrinogen-like proteins in Cancer

Yu, Jing; Li, Jing; Shen, Jing; Du, Fukuan; Wu, Xu; Li, Mingxing; Chen, Yu; Cho, Chi Hin; Li, Xiaobing; Xiao, Zhangang; Zhao, Yueshui

doi:10.7150/ijbs.56748

Cited by 27 publications

(29 citation statements)

References 89 publications

(145 reference statements)

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“… 28 Recently, overexpression of FGL1 has been reported in many solid tumors, and its expression is associated with a shorter 5-year overall survival rate. 29 The expression of FGL1 not only affects the regeneration of hepatocytes, but also regulates the growth and proliferation of tumor cells. 30 , 31 The research shows that FGL1 is the main inhibitory ligand of lymphocyte activation gene 3 (LAG-3), which can inhibit antigen-specific T cell responses through the interaction of FGL1/LAG-3.…”

Section: Introductionmentioning

confidence: 99%

Dual-targeting vaccine of FGL1/CAIX exhibits potent anti-tumor activity by activating DC-mediated multi-functional CD8 T cell immunity

Chai

Qin

Shi

et al. 2022

Molecular Therapy - Oncolytics

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Tumor DNA vaccine as an effective therapeutic approach can induce systemic immunity against malignant tumors, but its therapeutic effect is still not satisfactory in advanced renal cancer. Herein, a novel DNA vaccine containing dual antigens of fibrinogen-like protein 1 (FGL1) and carbonic anhydrase IX (CAIX) was developed and intramuscularly delivered by PLGA/PEI nanoparticles for renal cancer therapy. Compared with PLGA/PEI-pCAIX immunization, PLGA/PEI-pFGL1/pCAIX co-immunization significantly inhibited the subcutaneous tumor growth and promoted the differentiation and maturation of CD11c + DCs and CD11c + CD11b + DCs subset. Likewise, the increased capabilities of CD8 T cell proliferation, CTL responses, and multi-functional CD8 + T cell immune responses were observed in PLGA/PEI-pFGL1/pCAIX vaccine group. Interestingly, depletion of CD8 + T cells by using CD8 mAb resulted in a loss of anti-tumor function of PLGA/PEI-pFGL1/pCAIX vaccine, suggesting that the anti-tumor activity of the vaccine was dependent on CD8 + T cell immune responses. Furthermore, PLGA/PEI-pFGL1/pCAIX co-immunization also suppressed the lung metastasis of tumor mice by enhancing the multi-functional CD8 + T cell responses. Therefore, these results indicate that PLGA/PEI-pFGL1/pCAIX vaccine could provide an effective protective effect for renal cancer by enhanced DC-mediated multi-functional CD8 + T cell immune responses. This vaccine strategy offers a potential approach for solid or metastatic tumor treatment.

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Section: Introductionmentioning

confidence: 99%

Dual-targeting vaccine of FGL1/CAIX exhibits potent anti-tumor activity by activating DC-mediated multi-functional CD8 T cell immunity

Chai

Qin

Shi

et al. 2022

Molecular Therapy - Oncolytics

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show abstract

“…At present, studies on the regulation of FGL1 expression are not limited to the exploration of its physiological and pathological functions [ 87 ]. The expression of FGL1 in human solid tumors is different from that in paracancerous tissues.…”

Section: Role Of Fgl1 In Cancer Developmentmentioning

confidence: 99%

Fibrinogen-like protein 1 (FGL1): the next immune checkpoint target

Zhao

Wang

et al. 2021

J Hematol Oncol

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Immune checkpoint therapy has achieved significant efficacy by blocking inhibitory pathways to release the function of T lymphocytes. In the clinic, anti-programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) monoclonal antibodies (mAbs) have progressed to first-line monotherapies in certain tumor types. However, the efficacy of anti-PD-1/PD-L1 mAbs is still limited due to toxic side effects and de novo or adaptive resistance. Moreover, other immune checkpoint target and biomarkers for therapeutic response prediction are still lacking; as a biomarker, the PD-L1 (CD274, B7-H1) expression level is not as accurate as required. Hence, it is necessary to seek more representative predictive molecules and potential target molecules for immune checkpoint therapy. Fibrinogen-like protein 1 (FGL1) is a proliferation- and metabolism-related protein secreted by the liver. Multiple studies have confirmed that FGL1 is a newly emerging checkpoint ligand of lymphocyte activation gene 3 (LAG3), emphasizing the potential of targeting FGL1/LAG3 as the next generation of immune checkpoint therapy. In this review, we summarize the substantial regulation mechanisms of FGL1 in physiological and pathological conditions, especially tumor epithelial to mesenchymal transition, immune escape and immune checkpoint blockade resistance, to provide insights for targeting FGL1 in cancer treatment.

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“…However, research on membrane-type Fgl2 protein is mainly focused on the corresponding biological behaviour of its ability to cleave prothrombin into thrombin, while little is known about its role in cancers [12]. The expression of Fgl2 is significantly higher in many cancers, including colon cancer, oesophageal cancer, gastric cancer, breast cancer, lung cancer, and cervical cancer, but weakly expressed or not expressed in normal tissues adjacent to cancer [5]. Recent studies have reported that Fgl2 is overexpressed in hepatocellular carcinoma and that knocking down Fgl2 leads to inhibition of proliferation, which suggests that Fgl2 expression on cancer cells might be involved in tumour growth or other malignant biological behaviours [13].…”

Section: Ivyspringmentioning

confidence: 99%

“…Human fibroleukin 2 (Fgl2) is a member of the fibrinogen superfamily and has two different structural forms [5]. One is secreted-type Fgl2, which is the soluble form of Fgl2 and is mainly secreted by CD4 + CD25 + Foxp3 + regulatory T cells (Tregs) and…”

Section: Introductionmentioning

confidence: 99%

The Fgl2 interaction with Tyrobp promotes the proliferation of cutaneous squamous cell carcinoma by regulating ERK-dependent autophagy

Zeng¹,

Li²,

Chen³

et al. 2022

Int. J. Med. Sci.

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Human fibroleukin 2 (Fgl2), a member of the fibrinogen superfamily, can cleave prothrombin to generate thrombin or is secreted in a soluble form as a new type of effector of Tregs with immunomodulatory functions. However, there is little research on the role of Fgl2 in cutaneous squamous cell carcinoma (CSCC) growth. We examined the expression of Fgl2 in samples from CSCC patients and CSCC cell lines. Then, the effect of Fgl2 on CSCC was evaluated in vitro and in animals. Regulation of autophagy by Fgl2 was explored in CSCC. Coimmunoprecipitation (Co-IP) and immunofluorescence colocalization experiments were conducted to identify the regulatory effect of Fgl2 on the downstream protein Tyrobp. Then, gain-or loss-of-function analyses and evaluation of Tyrobp expression were performed to validate its role in autophagy and proliferation promoted by Fgl2. Here, our study demonstrated that Fgl2 promoted the proliferation of CSCC cells in vitro and in vivo. Knocking down Fgl2 reduced CSCC cell proliferation and inhibited autophagy in CSCC. Mechanistically, Fgl2 interacted with Tyrobp and promoted ERK-dependent autophagy, resulting in the proliferation of CSCC cells. Our study suggested that Fgl2 could be a promising prognostic biomarker and useful therapeutic target for CSCC.

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The role of Fibrinogen-like proteins in Cancer

Cited by 27 publications

References 89 publications

Dual-targeting vaccine of FGL1/CAIX exhibits potent anti-tumor activity by activating DC-mediated multi-functional CD8 T cell immunity

Dual-targeting vaccine of FGL1/CAIX exhibits potent anti-tumor activity by activating DC-mediated multi-functional CD8 T cell immunity

Fibrinogen-like protein 1 (FGL1): the next immune checkpoint target

The Fgl2 interaction with Tyrobp promotes the proliferation of cutaneous squamous cell carcinoma by regulating ERK-dependent autophagy

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