Casp6, also known as caspase-6, is a protease that plays a crucial role in cell pyroptosis and is involved in many cellular signaling pathways, such as the NLRP1-Casp1-Casp6 signaling pathway related to ischemic brain injury [1,3]. It is of great biological importance in processes like immune response, antigen processing and presentation [1]. Genetic models, including knockout mouse models, are valuable for studying its functions.

In glioma, Casp6 is overexpressed, correlated negatively with overall survival, and positively with the degree of glioma progression. In vitro experiments showed that knocking down Casp6 inhibited glioma cell proliferation, suggesting its role in glioma tumorigenesis [1]. In pancreatic adenocarcinoma, knockdown of Casp6 dramatically inhibited the proliferation, migration, and invasion ability of PANC-1 cells in vitro, indicating it could be a potential biomarker promoting the disease's occurrence and progression [2]. In B-lineage cells, Casp6 knockout mice had significantly more splenic B-cell subsets and dysregulated B-cell reconstitution after sublethal irradiation, suggesting Casp6 controls B-cell numbers during development [4]. Also, combined suppression of Casp6 and CASP2 in the optic nerve crush injury model promoted retinal ganglion cell axon regeneration through CNTF-mediated JAK/STAT signalling [5].

In conclusion, Casp6 is essential in processes like cell pyroptosis, immune response, and B-cell development. Studies using gene knockout models have revealed its significant roles in diseases such as glioma, pancreatic adenocarcinoma, and in conditions related to retinal ganglion cell injury, providing insights into potential therapeutic strategies for these diseases.

References:

1. Guo, Kai, Zhao, Jiahui, Jin, Qianxu, Shi, Yunpeng, Zhao, Zongmao. 2022. CASP6 predicts poor prognosis in glioma and correlates with tumor immune microenvironment. In Frontiers in oncology, 12, 818283. doi:10.3389/fonc.2022.818283. https://pubmed.ncbi.nlm.nih.gov/36119521/

2. Zhu, Jun, Shi, Yanlong, Lan, Sheng, Zhang, Yewei, Zhong, Fei. 2023. Dissection of pyroptosis-related prognostic signature and CASP6-mediated regulation in pancreatic adenocarcinoma: new sights to clinical decision-making. In Apoptosis : an international journal on programmed cell death, 28, 769-782. doi:10.1007/s10495-023-01823-7. https://pubmed.ncbi.nlm.nih.gov/36882663/

3. Ma, Zhuo, Li, Kai, Chen, Peng, Li, Xuyang, Zhao, Guoqing. . Propofol Attenuates Inflammatory Damage via Inhibiting NLRP1-Casp1-Casp6 Signaling in Ischemic Brain Injury. In Biological & pharmaceutical bulletin, 43, 1481-1489. doi:10.1248/bpb.b20-00050. https://pubmed.ncbi.nlm.nih.gov/32999158/

4. Watanabe, Chie, Shu, Geraldine L, Giltiay, Natalia V, Clark, Edward A. 2018. Regulation of B-lineage cells by caspase 6. In Immunology and cell biology, 96, 1072-1082. doi:10.1111/imcb.12172. https://pubmed.ncbi.nlm.nih.gov/29863787/

5. Vigneswara, Vasanthy, Akpan, Nsikan, Berry, Martin, Troy, Carol M, Ahmed, Zubair. 2014. Combined suppression of CASP2 and CASP6 protects retinal ganglion cells from apoptosis and promotes axon regeneration through CNTF-mediated JAK/STAT signalling. In Brain : a journal of neurology, 137, 1656-75. doi:10.1093/brain/awu037. https://pubmed.ncbi.nlm.nih.gov/24727569/