ACAP1, short for Arfgap with Coil-coil, Ankryin repeat, and PH domain I, is a crucial protein involved in endocytic recycling. It assembles into an unusual protein lattice for membrane deformation [2]. This process is essential for the normal function of lymphocytes and is associated with pathways like the Rab10-ACAP1-Arf6 GTPases cascade which modulates M4 muscarinic acetylcholine receptor trafficking and signaling [3]. ACAP1 also has a role in the regulation of FGFR2 phosphorylation in cholangiocarcinoma [4].

In solid tumors, ACAP1 deficiency predicts an inferior immunotherapy response. ACAP1 is highly expressed in immune-related tissues and cells, especially in tumor-infiltrating lymphocytes (TILs). Its deficiency is associated with poor prognosis and resistance to checkpoint blockade therapy. Functionally, depletion of ACAP1 by RNA interference impairs T cell-mediated killing of tumor cells [1]. In ovarian cancer, high ACAP1 expression predicts poor prognosis and is correlated with immune infiltration levels and immune-related pathways [5]. In lung adenocarcinoma, low ACAP1 expression is linked to unsatisfactory survival, and overexpression of ACAP1 attenuates cell proliferation, migration, and invasion [6].

In conclusion, ACAP1 is essential for endocytic recycling and the normal function of lymphocytes. Its deficiency has significant implications in cancer, especially in relation to immunotherapy response and prognosis. Studies on ACAP1 using models like RNA interference-mediated depletion have revealed its critical role in tumor-immune interactions, providing potential insights for cancer treatment strategies.

References:

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. Chan, Chun, Pang, Xiaoyun, Zhang, Yan, Sun, Fei, Fan, Jun. 2019. ACAP1 assembles into an unusual protein lattice for membrane deformation through multiple stages. In PLoS computational biology, 15, e1007081. doi:10.1371/journal.pcbi.1007081. https://pubmed.ncbi.nlm.nih.gov/31291238/

3. Xu, Rongmei, Wan, Min, Shi, Xuemeng, Yi, Ping, Zhang, Rongying. 2023. A Rab10-ACAP1-Arf6 GTPases cascade modulates M4 muscarinic acetylcholine receptor trafficking and signaling. In Cellular and molecular life sciences : CMLS, 80, 87. doi:10.1007/s00018-023-04722-x. https://pubmed.ncbi.nlm.nih.gov/36917255/

4. Zhao, Liming, Liu, Jialiang, Li, Kangshuai, Zhang, Zongli, Xu, Yunfei. 2023. PTPN9 dephosphorylates FGFR2 pY656/657 through interaction with ACAP1 and ameliorates pemigatinib effect in cholangiocarcinoma. In Hepatology (Baltimore, Md.), 79, 798-812. doi:10.1097/HEP.0000000000000552. https://pubmed.ncbi.nlm.nih.gov/37505213/

5. 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/

6. 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/