Akip1-KO Mouse

Akip1, or A Kinase Interacting Protein 1, is a signaling adaptor involved in multiple cellular processes. It has been associated with various pathways such as NF-κB, AKT, Wnt/β-catenin, and is crucial for physiological cardiac remodelling and also plays a significant role in cancer-related processes [1,5,6]. In cancer, it is linked to tumorigenesis, metastasis, angiogenesis, and chemoradiotherapy resistance [1,2,3,4,5,7,8]. Genetic models are valuable in studying Akip1's function as they can help elucidate its role in normal and disease-related biological processes.

In glioblastoma, down-regulating Akip1 impaired cell proliferation, colony formation, and tumorigenicity. Akip1 stabilizes EGFR by cooperating with YY1-mediated HSP90AA1 transcriptional activation [1]. In endometrial carcinoma, elevated Akip1 expression was associated with tumor invasion, shorter survival, and decreased chemosensitivity, and silencing Akip1 enhanced cisplatin sensitivity in Ishikawa cells [2]. In glioblastoma again, Akip1 promoted cell viability, mobility, and chemoradiation resistance via regulating CXCL1 and CXCL8 mediated NF-κB and AKT pathways [3]. In tongue squamous cell carcinoma, overexpression of Akip1 increased cell proliferation, migration, and invasion, and mRNA sequencing revealed its involvement in mTOR, PI3K-Akt, MAPK, Hippo, and Wnt signaling pathways [4]. In hepatocellular carcinoma, Akip1 promoted early recurrence by activating the Wnt/β-catenin/CBP signaling pathway [5].

In conclusion, Akip1 has diverse functions in both normal physiological processes like cardiac remodelling and in disease, especially cancer. Through gene-knockout or knockdown models in various cancer types, its role in promoting tumor progression, metastasis, and influencing chemosensitivity has been revealed. These findings highlight the importance of Akip1 as a potential therapeutic target in cancer treatment.

References:

1. Wan, Sicheng, Liu, Chaolong, Li, Chongyang, Zhang, Li, Cui, Hongjuan. 2023. AKIP1 accelerates glioblastoma progression through stabilizing EGFR expression. In Oncogene, 42, 2905-2918. doi:10.1038/s41388-023-02796-2. https://pubmed.ncbi.nlm.nih.gov/37596322/

2. Li, Aili, Li, Aijing, Gao, Xiangpeng, Xiao, Yalin, Zhao, Fei. 2022. Elevated AKIP1 expression is associated with tumor invasion, shorter survival time and decreased chemosensitivity in endometrial carcinoma. In Oncology letters, 24, 268. doi:10.3892/ol.2022.13388. https://pubmed.ncbi.nlm.nih.gov/35782897/

3. Han, Dayong, Zhang, Na, Zhao, Shu, Liu, Zhanwen, Teng, Lei. 2021. AKIP1 promotes glioblastoma viability, mobility and chemoradiation resistance via regulating CXCL1 and CXCL8 mediated NF-κB and AKT pathways. In American journal of cancer research, 11, 1185-1205. doi:. https://pubmed.ncbi.nlm.nih.gov/33948353/

4. Wang, Ning, Bai, Dan, Kristiansen, Einar, Deng, Ruoyu, Zhang, Shijun. 2021. AKIP1 promotes tumor progression by cancer-related pathways and predicts prognosis in tongue squamous cell carcinoma. In American journal of translational research, 13, 12338-12351. doi:. https://pubmed.ncbi.nlm.nih.gov/34956456/

5. Cui, Yanmei, Wu, Xianqiu, Lin, Chuyong, Guan, Jian, Song, Libing. 2019. AKIP1 promotes early recurrence of hepatocellular carcinoma through activating the Wnt/β-catenin/CBP signaling pathway. In Oncogene, 38, 5516-5529. doi:10.1038/s41388-019-0807-5. https://pubmed.ncbi.nlm.nih.gov/30936461/

6. Nijholt, Kirsten T, Sánchez-Aguilera, Pablo I, Booij, Harmen G, Silljé, Herman H W, Westenbrink, B Daan. 2023. A Kinase Interacting Protein 1 (AKIP1) promotes cardiomyocyte elongation and physiological cardiac remodelling. In Scientific reports, 13, 4046. doi:10.1038/s41598-023-30514-1. https://pubmed.ncbi.nlm.nih.gov/36899057/

7. Zhang, Wenying, Wu, Qiongwei, Wang, Chao, Liu, Ping, Ma, Chengbin. 2018. AKIP1 promotes angiogenesis and tumor growth by upregulating CXC-chemokines in cervical cancer cells. In Molecular and cellular biochemistry, 448, 311-320. doi:10.1007/s11010-018-3335-7. https://pubmed.ncbi.nlm.nih.gov/29520695/

8. Guo, Xiaobin, Zhao, Limin, Cheng, Dongjun, Kuang, Hongyan, Feng, Keqing. 2017. AKIP1 promoted epithelial-mesenchymal transition of non-small-cell lung cancer via transactivating ZEB1. In American journal of cancer research, 7, 2234-2244. doi:. https://pubmed.ncbi.nlm.nih.gov/29218247/