Cstb, also known as cystatin B, is an endogenous inhibitor of cathepsin proteases. It is involved in multiple biological processes, and its dysregulation is associated with various diseases. The ERK/AKT/mTOR signaling pathway has been linked to increased Cstb expression in hepatocellular carcinoma (HCC), suggesting its role in relevant pathways [1,2].

In HCC, silencing Cstb suppresses cellular proliferation by inducing cell cycle arrest in the G2 phase and impairs cell invasion and migration by stimulating epithelial-mesenchymal transition (EMT), revealing its oncogenic role in this cancer type [1]. In pancreatic ductal adenocarcinoma (PDAC), CSTB knockdown attenuates cell proliferation, as it increases autophagic flux and fuels glycolysis [3]. In murine type 1 progressive myoclonus epilepsy, CSTB gene replacement in knockout mice significantly improves neuroinflammatory pathway gene expression, cerebellar granule cell layer apoptosis, and motor impairment, indicating its importance in this neurodegenerative disease [4].

In conclusion, Cstb plays crucial roles in multiple biological processes and disease conditions. Gene knockout and gene replacement models in mice have provided insights into its functions in diseases such as HCC, PDAC, and progressive myoclonus epilepsy, highlighting its potential as a therapeutic target in these areas.

References:

1. Zhu, Weiyi, Dong, Xiangjun, Tian, Na, Zhou, Weihui, Song, Weihong. 2023. CSTB accelerates the progression of hepatocellular carcinoma via the ERK/AKT/mTOR signaling pathway. In Heliyon, 10, e23506. doi:10.1016/j.heliyon.2023.e23506. https://pubmed.ncbi.nlm.nih.gov/38187282/

2. Zhu, Weiyi, Dong, Xiangjun, Luo, Shuyue, Zhou, Weihui, Song, Weihong. 2023. Transcriptional activation of CSTB gene expression by transcription factor Sp3. In Biochemical and biophysical research communications, 649, 71-78. doi:10.1016/j.bbrc.2023.01.087. https://pubmed.ncbi.nlm.nih.gov/36745972/

3. Jiang, Yongsheng, Han, Lijie, Xue, Meilin, Jiang, Lingxi, Chen, Hao. . Cystatin B increases autophagic flux by sustaining proteolytic activity of cathepsin B and fuels glycolysis in pancreatic cancer: CSTB orchestrates autophagy and glycolysis in PDAC. In Clinical and translational medicine, 12, e1126. doi:10.1002/ctm2.1126. https://pubmed.ncbi.nlm.nih.gov/36495123/

4. Gumusgoz, Emrah, Kasiri, Sahba, Verma, Mayank, Gray, Steven J, Minassian, Berge A. 2023. CSTB gene replacement improves neuroinflammation, neurodegeneration and ataxia in murine type 1 progressive myoclonus epilepsy. In Gene therapy, 31, 234-241. doi:10.1038/s41434-023-00433-x. https://pubmed.ncbi.nlm.nih.gov/38135787/