Agbl2-KO Mouse

AGBL2, the ATP/GTP binding protein like 2, has been reported to catalyze α-tubulin detyrosination, which is involved in multiple cellular processes. This function may be related to various biological pathways, and it has potential importance in normal physiological and disease-related biological processes [2,3]. Genetic models could be valuable in further exploring its functions.

In renal cell carcinoma (RCC), TCGA analysis showed increased AGBL2 expression, correlated with poorer survival. Knockdown of AGBL2 in RCC cells inhibited cell proliferation and migration, while overexpression increased these processes. AGBL2 was also found to enhance AKT phosphorylation, and its detyrosination effect on α-tubulin was verified using a tubulin carboxypeptidase inhibitor. Additionally, AGBL2 was associated with immune infiltration in RCC [1].

In hepatocellular carcinoma (HCC), overexpression of AGBL2 in cell lines enhanced cell survival, proliferation in vitro and tumor growth in vivo, inhibited apoptosis through IRGM-regulated autophagy, and up-regulated TPX2 and Aurora A activity to promote cell proliferation [2].

In ovarian carcinoma, high AGBL2 expression was associated with tumor histological grade, advanced stages, and shorter patient survival, and was identified as an independent prognostic factor [3].

In breast and gastric cancer, AGBL2 was related to clinicopathological parameters, prognosis, cell proliferation, and chemotherapy resistance, and it could form immune complexes with its inhibitor latexin [4,5].

In summary, AGBL2 plays significant roles in multiple cancer types, including promoting cancer cell proliferation, migration, and affecting apoptosis and chemotherapy resistance through various mechanisms. Studies using cell lines and patient samples have revealed its potential as a prognostic marker and therapeutic target in cancers, providing valuable insights into understanding cancer pathogenesis and developing new treatment strategies.

References:

1. Liu, Wei, Zhang, Yifei, Nie, Yechen, Gong, Binbin, Ma, Ming. 2024. AGBL2 promotes renal cell carcinoma cells proliferation and migration via α-tubulin detyrosination. In Heliyon, 10, e37086. doi:10.1016/j.heliyon.2024.e37086. https://pubmed.ncbi.nlm.nih.gov/39315218/

2. Wang, Li-Li, Jin, Xiao-Han, Cai, Mu-Yan, Liu, Fang, Xie, Dan. 2017. AGBL2 promotes cancer cell growth through IRGM-regulated autophagy and enhanced Aurora A activity in hepatocellular carcinoma. In Cancer letters, 414, 71-80. doi:10.1016/j.canlet.2017.11.003. https://pubmed.ncbi.nlm.nih.gov/29126912/

3. He, Wei-Peng, Wang, Li-Li. 2019. High expression of AGBL2 is a novel prognostic factor of adverse outcome in patients with ovarian carcinoma. In Oncology letters, 18, 4900-4906. doi:10.3892/ol.2019.10829. https://pubmed.ncbi.nlm.nih.gov/31612000/

4. Zhang, Hao, Ren, Yuan, Pang, Deyan, Liu, Caigang. 2014. Clinical implications of AGBL2 expression and its inhibitor latexin in breast cancer. In World journal of surgical oncology, 12, 142. doi:10.1186/1477-7819-12-142. https://pubmed.ncbi.nlm.nih.gov/24884516/

5. Zhu, Haitao, Zheng, Zhichao, Zhang, Jianjun, Su, Xiaohui, Gu, Xiaohu. . Effects of AGBL2 on cell proliferation and chemotherapy resistance of gastric cancer. In Hepato-gastroenterology, 62, 497-502. doi:. https://pubmed.ncbi.nlm.nih.gov/25916089/