Abhd17c-KO Mouse

ABHD17C, an enzyme belonging to the ABHD17 family, is involved in the process of depalmitoylation, specifically removing S-palmitoylation from proteins like N-RAS [1,4]. This process is associated with the regulation of subcellular localization and function of targeted proteins, and is linked to the PI3K/AKT signaling pathway, which is crucial in cell growth, survival, and metabolism [1]. It also plays a role in metabolic and immune-related processes, potentially reshaping the tumor immunosuppressive microenvironment [2].

In hepatocellular carcinoma (HCC) cells, knockdown of USP35, which stabilizes ABHD17C, led to decreased ABHD17C protein level, impaired PI3K/AKT pathway, reduced proliferation, cell cycle arrest, increased apoptosis, and mitigated migration and invasion [1]. In pancreatic cancer, ABHD17C was identified as a potential biomarker for predicting prognosis and response to anti-PD1 therapy. Overexpression of ABHD17C in vivo significantly mediated resistance to anti-PD1 therapy and promoted pancreatic cancer progression [2]. Also, in pancreatic cancer, lncRNA MIR4435-2HG promotes cancer progression by regulating ABHD17C through sponging miR-128-3p [3].

In conclusion, ABHD17C is a key enzyme in depalmitoylation with significant implications in cancer-related biological processes. Studies using in vivo models in HCC and pancreatic cancer have revealed its role in promoting cancer development, highlighting its potential as a therapeutic target in these disease areas.

References:

1. Wang, Linpei, Wang, Jiawei, Ma, Xiaoqiu, Wang, Wei, Wu, Jian. 2023. USP35 promotes HCC development by stabilizing ABHD17C and activating the PI3K/AKT signaling pathway. In Cell death discovery, 9, 421. doi:10.1038/s41420-023-01714-5. https://pubmed.ncbi.nlm.nih.gov/37993419/

2. Zhang, Weihao, Xie, Yongjie, Yu, Xin, Xing, Wenge, Si, Tongguo. 2023. ABHD17C, a metabolic and immune-related gene signature, predicts prognosis and anti-PD1 therapy response in pancreatic cancer. In Discover oncology, 14, 87. doi:10.1007/s12672-023-00690-7. https://pubmed.ncbi.nlm.nih.gov/37273016/

3. Chen, Zhou, Du, Yan, Shi, Huaqing, He, Ru, Zhou, Wence. 2024. Long non-coding RNA MIR4435-2HG promotes pancreatic cancer progression by regulating ABHD17C through sponging miR-128-3p. In Translational cancer research, 13, 4113-4130. doi:10.21037/tcr-24-51. https://pubmed.ncbi.nlm.nih.gov/39262472/

4. Lin, David Tse Shen, Davis, Nicholas G, Conibear, Elizabeth. 2017. Targeting the Ras palmitoylation/depalmitoylation cycle in cancer. In Biochemical Society transactions, 45, 913-921. doi:10.1042/BST20160303. https://pubmed.ncbi.nlm.nih.gov/28630138/