Astn1-KO Mouse

Astn1, short for Astrotactin 1, is a gene known for its physiological role in neuronal migration [1,3]. It has been associated with the Wnt/β -catenin signaling pathway, with its levels negatively influencing this pathway [1]. It is also important in the context of various biological processes and disease conditions. Genetic models, such as gene knockout models, can be valuable for studying its functions.

In hepatocellular carcinoma (HCC), Astn1 levels are lower in cancer tissues compared to normal tissues. Its overexpression in liver cancer cell lines reduces cell migratory and invasive capacity via suppressing the Wnt/β -catenin signaling pathway, as indicated by downregulated protein levels of related factors like β -catenin, TCF1, C -myc, etc. In vivo, overexpression of Astn1 in xenografts reduces cancer development and Wnt signaling. Also, its expression is negatively correlated with B cell, macrophage, and neutrophil infiltrating levels in HCC [1]. In a study of Schwann cells, miR -sc3 promotes cell proliferation and migration by directly targeting Astn1, leading to its translational suppression, suggesting a role in peripheral nerve regeneration [2].

In conclusion, Astn1 plays a crucial role in neuronal migration and is involved in regulating cell migration and invasion in liver cancer through the Wnt/β -catenin signaling pathway. Its study in various models helps to understand biological processes like peripheral nerve regeneration and disease mechanisms in cancer, providing potential insights for diagnosis, prognosis, and treatment strategies.

References:

1. Chen, Qi-Feng, Shi, Feng, Huang, Tao, Wu, Peihong, Li, Wang. 2020. ASTN1 is associated with immune infiltrates in hepatocellular carcinoma, and inhibits the migratory and invasive capacity of liver cancer via the Wnt/β‑catenin signaling pathway. In Oncology reports, 44, 1425-1440. doi:10.3892/or.2020.7704. https://pubmed.ncbi.nlm.nih.gov/32945491/

2. Yi, Sheng, Wang, Shanshan, Zhao, Qing, Gu, Xiaosong, Li, Shiying. 2016. miR-sc3, a Novel MicroRNA, Promotes Schwann Cell Proliferation and Migration by Targeting Astn1. In Cell transplantation, 25, 973-82. doi:10.3727/096368916X690520. https://pubmed.ncbi.nlm.nih.gov/26786955/

3. Wilson, Perrin M, Fryer, Robert H, Fang, Yin, Hatten, Mary E. . Astn2, a novel member of the astrotactin gene family, regulates the trafficking of ASTN1 during glial-guided neuronal migration. In The Journal of neuroscience : the official journal of the Society for Neuroscience, 30, 8529-40. doi:10.1523/JNEUROSCI.0032-10.2010. https://pubmed.ncbi.nlm.nih.gov/20573900/