Anxa8, a member of the annexins family, encodes an anticoagulant protein involved in blood coagulation cascade and acts as an indirect inhibitor of the thromboplastin-specific complex [2]. It has been associated with multiple cellular processes including proliferation, metastasis, and inflammation, and is involved in various signaling pathways such as EGFR-AKT-mTOR, Wnt/β-catenin, and EGF-FOXO4 [1,3,5]. Its study through genetic models like KO/CKO mouse models can help uncover its role in different biological processes and diseases.

In a study on atherosclerosis-prone apolipoprotein E (ApoE-/-) mice, germline deletion of Anxa8 decreased the atherosclerotic burden, plaque size, and macrophage accumulation [4]. The plaques in ApoE-/-Anxa8-/-mice had lower lipid and inflammatory content, smaller necrotic core, thicker fibrous cap, and less apoptosis compared to ApoE-/-Anxa8 + / + mice. Also, endothelial-specific silencing of Anxa8 decreased atherosclerosis progression. In another study, injection of mus-siRNA-ANXA8 into the uterine horn of mice significantly reduced the number of implantation sites, suggesting that ANXA8 promotes the proliferation of endometrial cells through the Akt signalling pathway [2]. In ovarian cancer cells, interference with ANXA8 inhibited the malignant progression by suppressing the activation of the Wnt/β-catenin signaling pathway via UCHL5 [3].

In conclusion, Anxa8 plays crucial roles in processes like cell proliferation, metastasis, and inflammation. Gene-knockout mouse models have revealed its significance in diseases such as atherosclerosis, endometrial cell function, and ovarian cancer. Understanding Anxa8's functions through these models provides insights into disease mechanisms and potential therapeutic strategies for related diseases.

References:

1. Zhou, G-Z, Sun, Y-H, Shi, Y-Y, Cui, L-Q, Sun, G-C. . [ANXA8 Regulates Proliferation of Human Non-Small Lung Cancer Cells A549 via EGFR-AKT-mTOR Signaling Pathway]. In Molekuliarnaia biologiia, 55, 870-880. doi:10.31857/S0026898421050116. https://pubmed.ncbi.nlm.nih.gov/34671007/

2. Jiang, Xiaona, Xue, Songyi, Kang, Tingting, Ni, Debin, Lei, Minggang. 2018. Annexin A8 (ANXA8) regulates proliferation of porcine endometrial cells via Akt signalling pathway. In Reproduction in domestic animals = Zuchthygiene, 54, 3-10. doi:10.1111/rda.13280. https://pubmed.ncbi.nlm.nih.gov/30040162/

3. Xu, Li, Wang, Liang, Gan, Yaping, Ning, Yingxia, Feng, Weifeng. 2024. Interference with ANXA8 inhibits the malignant progression of ovarian cancer by suppressing the activation of the Wnt/β-catenin signaling pathway via UCHL5. In Aging, 16, 11275-11288. doi:10.18632/aging.205991. https://pubmed.ncbi.nlm.nih.gov/39068672/

4. Gutiérrez-Muñoz, Carmen, Blázquez-Serra, Rafael, San Sebastian-Jaraba, Irene, Méndez-Barbero, Nerea, Blanco-Colio, Luis M. . Annexin A8 deficiency delays atherosclerosis progression. In Clinical and translational medicine, 15, e70176. doi:10.1002/ctm2.70176. https://pubmed.ncbi.nlm.nih.gov/39835780/

5. Lee, Mi-Jin, Yu, Gyung-Ran, Yoo, Hee-Jung, Choi, Yang-Kyu, Kim, Dae-Ghon. 2009. ANXA8 down-regulation by EGF-FOXO4 signaling is involved in cell scattering and tumor metastasis of cholangiocarcinoma. In Gastroenterology, 137, 1138-50, 1150.e1-9. doi:10.1053/j.gastro.2009.04.015. https://pubmed.ncbi.nlm.nih.gov/19376120/