Department of Cardiothoracic Surgery, Sichuan Mianyang 404 Hospital, Mianyang City, Sichuan Province, China.
Clin Respir J. 2024 Aug;18(8):e13825. doi: 10.1111/crj.13825.
Lung adenocarcinoma (LUAD) is a fatal disease with metabolic abnormalities. The dysregulation of S100 calcium-binding protein A2 (S100A2), a member of the S100 protein family, is connected to the development of various cancers. The impact of S100A2 on the LUAD occurrence and metastasis, however, has not yet been reported. The functional mechanism of S100A2 on LUAD cell metastasis was examined in this article.
The expression of TFAP2A and S100A2 in LUAD tissues and cells was analyzed by bioinformatics and qRT-PCR, respectively. The enrichment pathway analysis was performed on S100A2. Bioinformatics analysis determined the binding relationship between TFAP2A and S100A2, and their interaction was validated through dual-luciferase and chromatin immunoprecipitation experiments. Cell viability was determined using cell counting kit-8 (CCK-8). A transwell assay was performed to analyze the invasion and migration of cells. Immunofluorescence was conducted to obtain vimentin and E-cadherin expression, and a western blot was used to detect the expression of MMP-2, MMP-9, GLS, and GLUD1. The kits measured the NADPH/NADP ratio, glutathione (GSH)/glutathione disulfide (GSSG) levels, and the contents of glutamine, α-KG, and glutamate.
S100A2 was upregulated in LUAD tissues and cells, and S100A2 mediated glutamine metabolism to induce LUAD metastasis. Additionally, the transcriptional regulator TFAP2A was discovered upstream of S100A2, and TFAP2A expression was upregulated in LUAD, which indicated that TFAP2A promoted the S100A2 expression. The rescue experiment found that upregulation of S100A2 could reverse the inhibitory effects of silencing TFAP2A on glutamine metabolism and cell metastasis.
In conclusion, by regulating glutamine metabolism, the TFAP2A/S100A2 axis facilitated LUAD metastasis. This suggested that targeting S100A2 could be beneficial for LUAD treatment.
肺腺癌 (LUAD) 是一种具有代谢异常的致命疾病。S100 钙结合蛋白 A2（S100A2）是 S100 蛋白家族的成员，其失调与各种癌症的发展有关。然而，S100A2 对 LUAD 发生和转移的影响尚未见报道。本文研究了 S100A2 对 LUAD 细胞转移的功能机制。
通过生物信息学和 qRT-PCR 分别分析 LUAD 组织和细胞中 TFAP2A 和 S100A2 的表达。对 S100A2 进行富集通路分析。生物信息学分析确定了 TFAP2A 和 S100A2 之间的结合关系，并通过双荧光素酶和染色质免疫沉淀实验验证了它们的相互作用。使用细胞计数试剂盒-8 (CCK-8) 测定细胞活力。通过 Transwell 分析测定细胞的侵袭和迁移。免疫荧光法获取波形蛋白和 E-钙黏蛋白的表达，Western blot 检测 MMP-2、MMP-9、GLS 和 GLUD1 的表达。试剂盒测定 NADPH/NADP 比、谷胱甘肽 (GSH)/谷胱甘肽二硫化物 (GSSG) 水平以及谷氨酰胺、α-KG 和谷氨酸的含量。
S100A2 在 LUAD 组织和细胞中上调，S100A2 通过调节谷氨酰胺代谢诱导 LUAD 转移。此外，发现 S100A2 的上游转录调节因子 TFAP2A 在 LUAD 中上调，表明 TFAP2A 促进了 S100A2 的表达。挽救实验发现，上调 S100A2 可以逆转沉默 TFAP2A 对谷氨酰胺代谢和细胞转移的抑制作用。
总之，通过调节谷氨酰胺代谢，TFAP2A/S100A2 轴促进了 LUAD 转移。这表明靶向 S100A2 可能有助于 LUAD 的治疗。
