The Fg12 interaction with Tyrobp promotes the proliferation of cutaneous squamous cell carcinoma by regulating ERK-dependent autophagy

作者：Zeng, Mei; Li, Qingxiang; Chen, Junzhao; Huang, Wenfu; Liu, Jinhua; Wang, Cuiyan; Huang, Manni; Li, Hui; Zhou, Shu; Xie, Miaoying; Zeng, Kang^*

来源：International Journal of Medical Sciences, 2022, 19(1): 195-204.

DOI：10.7150/ijms.66929

• Cutaneous squamous cell carcinoma
• Fg12
• Tyrobp
• proliferation
• autophagy

Human fibroleukin 2 (Fg12), 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 Fg12 in cutaneous squamous cell carcinoma (CSCC) growth. We examined the expression of Fg12 in samples from CSCC patients and CSCC cell lines. Then, the effect of Fg12 on CSCC was evaluated in vitro and in animals. Regulation of autophagy by Fg12 was explored in CSCC. Coimmunoprecipitation (Co-IP) and immunofluorescence colocalization experiments were conducted to identify the regulatory effect of Fg12 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 Fg12. Here, our study demonstrated that Fg12 promoted the proliferation of CSCC cells in vitro and in vivo. Knocking down Fg12 reduced CSCC cell proliferation and inhibited autophagy in CSCC. Mechanistically, Fg12 interacted with Tyrobp and promoted ERK-dependent autophagy, resulting in the proliferation of CSCC cells. Our study suggested that Fg12 could be a promising prognostic biomarker and useful therapeutic target for CSCC.

• 单位
  南方医科大学