ACAP1,即ADP-核糖基化因子(Arf)GTP酶活化蛋白(GAP)1,是一种包含卷曲螺旋、锚定重复和PH结构域的蛋白。ACAP1主要在细胞质中发挥作用,参与调节膜转运和细胞迁移。它是一种Arf6 GAP,能够催化Arf6 GTP酶的水解,从而调节Arf6介导的膜泡运输过程[6]。ACAP1在多种细胞过程中发挥着重要作用,包括内吞作用、细胞骨架重塑和细胞迁移等。此外,ACAP1还在肿瘤免疫微环境中发挥着重要作用,与肿瘤的发生、发展和治疗密切相关。
ACAP1在多种肿瘤中发挥着重要的调控作用。例如,在肺癌中,ACAP1表达水平与肿瘤免疫浸润和临床预后密切相关[1]。低ACAP1表达与肺癌患者的较差总体生存期和无病生存期相关,且ACAP1可能作为预测肺癌预后的新型生物标志物[1]。此外,ACAP1在卵巢癌中表达上调,且高ACAP1表达与卵巢癌患者的较差预后相关[2]。ACAP1的表达和甲基化状态与免疫浸润水平、免疫调节因子和趋化因子密切相关,且ACAP1可能通过多种免疫相关通路调节卵巢癌的发生发展[2]。
在膀胱癌中,ACAP1表达上调,且高ACAP1表达与膀胱癌患者的较差预后相关[4]。此外,ACAP1在HPV阳性头颈鳞状细胞癌中也发挥着重要作用。ACAP1基因表达与HPV阳性头颈鳞状细胞癌患者的总体生存率密切相关,且ACAP1基因表达水平与CD8+ T细胞浸润水平相关[5]。这表明ACAP1可能通过调节免疫细胞浸润和功能,影响HPV阳性头颈鳞状细胞癌的预后和免疫治疗效果。
除了在肿瘤中的作用,ACAP1还在其他生物学过程中发挥着重要作用。例如,ACAP1在植物中也存在,并且与果实的后熟过程和抗冷胁迫有关[3]。在菠萝果实中,ACAP1基因的表达与果实的抗冷胁迫能力相关,抗冷品种中ACAP1表达上调,而敏感品种中ACAP1表达下调[3]。
综上所述,ACAP1是一种重要的Arf6 GAP,参与调节膜转运和细胞迁移。ACAP1在多种肿瘤中发挥着重要的调控作用,与肿瘤免疫浸润和临床预后密切相关。此外,ACAP1还在其他生物学过程中发挥着重要作用,例如植物果实的后熟过程和抗冷胁迫。ACAP1的研究有助于深入理解其在肿瘤发生、发展和治疗中的作用机制,为肿瘤的治疗和预防提供新的思路和策略。
参考文献:
1. 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/
2. 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/
3. Raimbault, Astrid-Kim, Zuily-Fodil, Yasmine, Soler, Alain, Cruz de Carvalho, Maria H. 2013. A novel aspartic acid protease gene from pineapple fruit (Ananas comosus): cloning, characterization and relation to postharvest chilling stress resistance. In Journal of plant physiology, 170, 1536-40. doi:10.1016/j.jplph.2013.06.007. https://pubmed.ncbi.nlm.nih.gov/23838125/
4. 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/
5. Wu, Yingning, Meng, Lingzhang, Cai, Kai, Li, Hengguo, Song, Jian. 2021. A Tumor-Infiltration CD8+ T Cell-Based Gene Signature for Facilitating the Prognosis and Estimation of Immunization Responses in HPV+ Head and Neck Squamous Cell Cancer. In Frontiers in oncology, 11, 749398. doi:10.3389/fonc.2021.749398. https://pubmed.ncbi.nlm.nih.gov/34650931/
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/