Expression of Cell Pyroptosis-Associated TLR4 Signalling Pathway During the Progression from Actinic Keratosis to Cutaneous Squamous Cell Carcinoma
10.12259/j.issn.2095-610X.S20251102
- VernacularTitle:细胞焦亡相关TLR4信号通路在光线性角化病向皮肤鳞癌进展中的表达
- Author:
Xiaoyu ZHAO
1
;
Minyan ZHANG
;
Huiya CHEN
;
Tingting CUI
;
Yuhan HUANG
;
Dan XU
Author Information
1. 昆明医科大学第一附属医院皮肤科,云南 昆明 650032
- Keywords:
Cutaneous squamous cell carcinoma;
Actinic keratosis;
Cell pyroptosis;
TLR4
- From:
Journal of Kunming Medical University
2025;46(11):11-17
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate whether the pyroptosis-related Toll-like receptor 4(TLR4)signaling pathway influences the malignant transformation of actinic keratosis(AK)into cutaneous squamous cell carcinoma(SCC).Methods A total of 6 lesion tissue samples each from patients with AK and SCC,as well as 5 normal skin tissue samples from healthy subjects as controls,were collected from the First Affiliated Hospital of Kunming Medical University between August 2020 and August 2021.Quantitative PCR(qPCR)and Western blot analysis were performed to determine the mRNA and protein expression levels of TLR4 pathway-related factors,including TLR4,CPB1,NLRP3,IL-1β,and IL-18.TLR4/TUNEL double immunofluorescence staining was used to evaluate TLR4 expression and the level of cellular pyroptosis in tissue samples.In addition,Western blotting was performed to analyze the expression differences of pyroptosis-related core proteins(pro-caspase-1,cleaved caspase-1/p20,GSDMD,and cleaved N-terminal GSDMD)and TLR4 among the normal keratinocyte cell line HaCaT and SCC cell lines A431 and SCL-1.Results Quantitative PCR and Western blot results showed that the mRNA and protein expression levels of TLR4,CPB1,NLRP3,IL-1β,and IL-18 were significantly higher in SCC tissues than in AK and normal skin tissues(P<0.05).TLR4/TUNEL double immunofluorescence results revealed a progressive increasing trend in TLR4 expression and pyroptosis levels from normal skin to AK and further to SCC(P<0.05).Furthermore,in SCL-1 cells,the expression levels of pro-caspase-1,cleaved caspase-1/p20,cleaved N-terminal GSDMD,and TLR4 were significantly upregulated(P<0.05),whereas in A431 cells,only TLR4 expression was increased(P<0.05),and the levels of other pyroptosis-related proteins were downregulated compared to HaCaT cells(P<0.05).Conclusion The expression of the TLR4 signaling pathway gradually increased from AK to SCC,and its activation status varied among different cutaneous squamous cell carcinoma cell lines.
