Int J Med Sci 2022; 19(1):195-204. doi:10.7150/ijms.66929 This issue

Research Paper

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

Mei Zeng1,2, Qingxiang Li1, Junzhao Chen1, Wenfu Huang1, Jinhua Liu1, Cuiyan Wang1, Manni Huang1, Hui Li1, Shu Zhou1, Miaoying Xie1, Kang Zeng2✉

1. Department of Dermatology, Huizhou Municipal Central Hospital, Huizhou 516000, Guangdong, People's Republic of China.
2. Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, People's Republic of China.

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Citation:
Zeng M, Li Q, Chen J, Huang W, Liu J, Wang C, Huang M, Li H, Zhou S, Xie M, Zeng K. The Fgl2 interaction with Tyrobp promotes the proliferation of cutaneous squamous cell carcinoma by regulating ERK-dependent autophagy. Int J Med Sci 2022; 19(1):195-204. doi:10.7150/ijms.66929. Available from https://www.medsci.org/v19p0195.htm

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Abstract

Graphic abstract

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.

Keywords: Cutaneous squamous cell carcinoma, Fgl2, Tyrobp, proliferation, autophagy