Skip to main content
Log in

Increased FGL1 Expression Predicts Poor Prognosis and Promotes EMT in Head and Neck Squamous Cell Carcinoma

  • Original Article
  • Published:
Biochemical Genetics Aims and scope Submit manuscript

Abstract

Fibrinogen-like protein 1 (FGL1) is a proliferation- and metabolism-related factor secreted by the liver that is aberrantly expressed and functionally abnormal in human malignancies. However, the role of FGL1 in head and neck squamous cell carcinoma (HNSCC) remains unknown. We analysed FGL1 expression in HNSCC and its impact on patient survival using the TCGA database. The role of FGL1 in HNSCC cells was investigated by Cell Counting Kit-8, colony formation, and Transwell assays. In addition, we conducted in vivo experiments to assess the effect of FGL1 knockdown on tumour growth. We found that FGL1 was highly expressed in HNSCC and correlated with a poor prognosis. Downregulation of FGL1 expression inhibited the proliferation and invasion of HNSCC cells. Furthermore, mechanistic analysis revealed that FGL1 induced an epithelial-mesenchymal transition (EMT) phenotype and, thus, the malignant progression of HNSCC cells. Finally, xenograft models showed that FGL1 knockdown significantly inhibited EMT in HNSCC in vivo. Our study revealed that FGL1, an oncogene, promotes the malignant progression of HNSCC, providing new perspective on and potential therapeutic target for the treatment of HNSCC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  • Banyard J, Bielenberg DR (2015) The role of EMT and MET in cancer dissemination. Connect Tissue Res 56:403–413

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bie F, Wang G, Qu X, Wang Y, Huang C, Wang Y et al (2019) Loss of FGL1 induces epithelial–mesenchymal transition and angiogenesis in LKB1 mutant lung adenocarcinoma. Int J Oncol 55:697–707

    CAS  PubMed  Google Scholar 

  • Castilho RM, Squarize CH, Almeida LO (2017) Epigenetic modifications and Head and Neck Cancer: implications for Tumor Progression and Resistance to Therapy. Int J Mol Sci, 18

  • Gao M, Zhan YQ, Yu M, Ge CH, Li CY, Zhang JH et al (2014) Hepassocin activates the EGFR/ERK cascade and induces proliferation of L02 cells through the src-dependent pathway. Cell Signal 26:2161–2166

    Article  CAS  PubMed  Google Scholar 

  • Greenberg AS, Coleman RA, Kraemer FB, McManaman JL, Obin MS, Puri V et al (2011) The role of lipid droplets in metabolic disease in rodents and humans. J Clin Invest 121:2102–2110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu Z, Ukomadu C (2008) Fibrinogen-like protein 1, a hepatocyte derived protein is an acute phase reactant. Biochem Biophys Res Commun 365:729–734

    Article  CAS  PubMed  Google Scholar 

  • Lv Z, Cui B, Huang X, Feng HY, Wang T, Wang HF et al (2021) FGL1 as a Novel Mediator and Biomarker of Malignant Progression in Clear Cell Renal Cell Carcinoma. Front Oncol 11:756843

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Michalopoulos GK, Bhushan B (2021) Liver regeneration: biological and pathological mechanisms and implications. Nat Rev Gastroenterol Hepatol 18:40–55

    Article  PubMed  Google Scholar 

  • Mikheeva SA, Mikheev AM, Petit A, Beyer R, Oxford RG, Khorasani L et al (2010) TWIST1 promotes invasion through mesenchymal change in human glioblastoma. Mol Cancer 9:194

    Article  PubMed  PubMed Central  Google Scholar 

  • Mittal V (2018) Epithelial mesenchymal transition in Tumor Metastasis. Annu Rev Pathol 13:395–412

    Article  CAS  PubMed  Google Scholar 

  • Mody MD, Rocco JW, Yom SS, Haddad RI, Saba NF (2021) Head and neck cancer. Lancet 398:2289–2299

    Article  PubMed  Google Scholar 

  • Qian W, Zhao M, Wang R, Li H (2021) Fibrinogen-like protein 1 (FGL1): the next immune checkpoint target. J Hematol Oncol 14:147

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sun C, Gao W, Liu J, Cheng H, Hao J (2020) FGL1 regulates acquired resistance to Gefitinib by inhibiting apoptosis in non-small cell lung cancer. Respir Res 21:210

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A et al (2021) Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and Mortality Worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71:209–249

    Article  PubMed  Google Scholar 

  • Tang XY, Xiong YL, Shi AP, Sun Y, Han Q, Lv Y et al (2022) The downregulation of fibrinogen-like protein 1 inhibits the proliferation of lung adenocarcinoma via regulating MYC-target genes. Transl Lung Cancer Res 11:404–419

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang J, Sanmamed MF, Datar I, Su TT, Ji L, Sun J et al (2019) Fibrinogen-like protein 1 is a major Immune Inhibitory ligand of LAG-3. Cell 176:334–347

    Article  CAS  PubMed  Google Scholar 

  • Wicki A, Lehembre F, Wick N, Hantusch B, Kerjaschki D, Christofori G (2006) Tumor invasion in the absence of epithelial-mesenchymal transition: podoplanin-mediated remodeling of the actin cytoskeleton. Cancer Cell 9:261–272

    Article  CAS  PubMed  Google Scholar 

  • Woo SR, Turnis ME, Goldberg MV, Bankoti J, Selby M, Nirschl CJ et al (2012) Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape. Cancer Res 72:917–927

    Article  CAS  PubMed  Google Scholar 

  • Yan Q, Lin HM, Zhu K, Cao Y, Xu XL, Zhou ZY et al (2022) Immune Checkpoint FGL1 expression of circulating Tumor cells is Associated with Poor Survival in Curatively Resected Hepatocellular Carcinoma. Front Oncol 12:810269

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang Y, Qiao HX, Zhou YT, Hong L, Chen JH (2018) Fibrinogen–like–protein 1 promotes the invasion and metastasis of gastric cancer and is associated with poor prognosis. Mol Med Rep 18:1465–1472

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou L, Xu N, Shibata H, Saloura V, Uppaluri R (2021) Epigenetic modulation of immunotherapy and implications in head and neck cancer. Cancer Metastasis Rev 40:141–152

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This study was funded by Natural Science Foundation of Fujian Province (2021J011373).

Author information

Authors and Affiliations

Authors

Contributions

Zhiyong Pan and Linwei Mao and developed methods, interpreted results, and wrote the manuscript, Weiqun Hu revised the manuscript, Pingping Wang and Zhicong Zheng prepared Figs. 1, 2, 3, 4 and 5 and Enrun Lin and Jinqiao Huang prepared Table 1, and 2. All authors reviewed and approved the manuscript.

Corresponding author

Correspondence to Linwei Mao.

Ethics declarations

Ethics Approval

Our research has obtained permission from the Institutional Ethics Committee of Affiliated Hospital of Putian University.

Competing interests

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pan, Z., Hu, W., Huang, J. et al. Increased FGL1 Expression Predicts Poor Prognosis and Promotes EMT in Head and Neck Squamous Cell Carcinoma. Biochem Genet (2023). https://doi.org/10.1007/s10528-023-10545-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s10528-023-10545-z

Keywords

Navigation