ACAP1,全称为ADP-ribosylation factor (Arf)-GTPase-activating protein (GAP) with coiled-coil, ankyrin repeat and PH domains 1,是一种重要的Arf6 GAP,参与调节内吞作用和细胞迁移。ACAP1在多种生物学过程中发挥作用,包括细胞分化、发育、代谢和疾病发生。
ACAP1在多种疾病中发挥重要作用。在肿瘤中,ACAP1的表达和功能与肿瘤免疫浸润和临床预后相关。例如,在肺癌中,ACAP1表达下调,与不良预后相关。在卵巢癌中,ACAP1表达上调,也与不良预后相关。此外,ACAP1的表达还与肿瘤免疫浸润和免疫检查点分子的表达相关,提示ACAP1可能参与调节肿瘤免疫微环境[3][4][5][6]。
在免疫系统中,ACAP1的表达和功能也与免疫细胞的正常功能相关。例如,ACAP1在淋巴组织中高表达,并与T细胞、B细胞和NK细胞的浸润相关。ACAP1的缺乏与肿瘤免疫治疗的反应不良相关,提示ACAP1可能参与调节TILs的正常功能,并影响肿瘤的免疫状态[1][7]。
ACAP1的表达和功能还与自身免疫性疾病相关。例如,ACAP1的表达下调与系统性红斑狼疮(SLE)相关。此外,ACAP1的表达还与CD83的表达相关,提示ACAP1可能参与调节SLE的发生和发展[2]。
综上所述,ACAP1是一种重要的Arf6 GAP,参与调节内吞作用和细胞迁移。ACAP1在多种生物学过程中发挥作用,包括细胞分化、发育、代谢和疾病发生。ACAP1在肿瘤、免疫系统和自身免疫性疾病中发挥重要作用,为疾病的治疗和预防提供新的思路和策略。
参考文献:
1. Yi, Qiyi, Pu, Youguang, Chao, Fengmei, Bian, Po, Lv, Lei. 2022. ACAP1 Deficiency Predicts Inferior Immunotherapy Response in Solid Tumors. In Cancers, 14, . doi:10.3390/cancers14235951. https://pubmed.ncbi.nlm.nih.gov/36497434/
2. Yin, Xianyong, Kim, Kwangwoo, Suetsugu, Hiroyuki, Cui, Yong, Bae, Sang-Cheol. 2022. Biological insights into systemic lupus erythematosus through an immune cell-specific transcriptome-wide association study. In Annals of the rheumatic diseases, 81, 1273-1280. doi:10.1136/annrheumdis-2022-222345. https://pubmed.ncbi.nlm.nih.gov/35609976/
3. Wang, Ning, Zhu, Lingye, Xu, Xiaomei, Yu, Chang, Huang, Xiaoying. 2022. Integrated analysis and validation reveal ACAP1 as a novel prognostic biomarker associated with tumor immunity in lung adenocarcinoma. In Computational and structural biotechnology journal, 20, 4390-4401. doi:10.1016/j.csbj.2022.08.026. https://pubmed.ncbi.nlm.nih.gov/36051873/
4. Zhang, Jiawen, Zhang, Qinyi, Zhang, Jing, Wang, Qingying. 2020. Expression of ACAP1 Is Associated with Tumor Immune Infiltration and Clinical Outcome of Ovarian Cancer. In DNA and cell biology, 39, 1545-1557. doi:10.1089/dna.2020.5596. https://pubmed.ncbi.nlm.nih.gov/32456571/
5. Wang, Zhi, Tu, Lei, Chen, Minfeng, Tong, Shiyu. 2021. Identification of a tumor microenvironment-related seven-gene signature for predicting prognosis in bladder cancer. In BMC cancer, 21, 692. doi:10.1186/s12885-021-08447-7. https://pubmed.ncbi.nlm.nih.gov/34112144/
6. Jackson, T R, Brown, F D, Nie, Z, Donaldson, J G, Randazzo, P A. . ACAPs are arf6 GTPase-activating proteins that function in the cell periphery. In The Journal of cell biology, 151, 627-38. doi:. https://pubmed.ncbi.nlm.nih.gov/11062263/
7. Choy, Chi Tung, Wong, Chi Hang, Chan, Stephen Lam. 2019. Embedding of Genes Using Cancer Gene Expression Data: Biological Relevance and Potential Application on Biomarker Discovery. In Frontiers in genetics, 9, 682. doi:10.3389/fgene.2018.00682. https://pubmed.ncbi.nlm.nih.gov/30662451/