Atp6v1c1-KO Mouse

Atp6v1c1, the ATPase H+ transporting V1 subunit C1, is a subunit gene of vacuolar adenosine triphosphatase (V-ATPase). V-ATPase is crucial for proper lumen acidification in many organelles, and its proton-pumping action is involved in various biological processes. It may also be associated with the mTORC1 signaling pathway [1].

In various disease models, Atp6v1c1 has shown significant impacts. In hepatocellular carcinoma (HCC), its high expression in tumor tissues is related to poor prognosis, and knockdown of Atp6v1c1 impairs HCC cell proliferation, migration, and invasion by down-regulating the mTORC1 signaling pathway [1]. In breast cancer cells, depletion of Atp6v1c1 disrupts the normal arrangement of filamentous actin, suggesting its role in breast cancer metastasis [2]. In a mouse model of periodontitis, AAV-mediated Atp6v1c1 knockdown gene therapy can prevent bone erosion and gingival inflammation, reducing osteoclast numbers and inhibiting immune cell infiltration [3]. In esophageal squamous cell carcinoma, suppressing Atp6v1c1 increases the sensitivity of cancer cells to radiotherapy and promotes autophagy [4]. In breast cancer, silencing Atp6v1c1 inhibits lysosomal acidification, impairs cell growth, migration, and invasion, and suppresses tumor growth and metastasis in vivo [5]. In osteoclasts, Atp6v1c1-silencing by lentivirus-mediated RNA interference severely impairs osteoclast acidification activity and bone resorption, and affects F-actin ring formation [6].

In conclusion, Atp6v1c1 is essential for multiple biological processes. Its role in diseases such as cancers (hepatocellular, breast, esophageal squamous cell carcinoma) and periodontitis has been revealed through gene-knockdown and other model-based studies. These findings suggest Atp6v1c1 could be a potential therapeutic target for treating these diseases.

References:

1. Pan, Yuhao, Chen, Hao, Lv, Chenhui, Xu, Yongpeng, Xuan, Qijia. 2024. ATP6V1C1, associated with the tumor microenvironment and mTORC1 signaling pathway, is a potential diagnostic, prognostic, and therapeutic biomarker for hepatocellular carcinoma. In Discover oncology, 15, 673. doi:10.1007/s12672-024-01578-w. https://pubmed.ncbi.nlm.nih.gov/39557733/

2. Cai, Ming, Liu, Pengcheng, Wei, Li, Feng, Shengmei, Deng, Lianfu. 2014. Atp6v1c1 may regulate filament actin arrangement in breast cancer cells. In PloS one, 9, e84833. doi:10.1371/journal.pone.0084833. https://pubmed.ncbi.nlm.nih.gov/24454753/

3. Li, Sheng, Hao, Liang, Wang, Lin, Shao, Jian-Zhong, Chen, Wei. 2015. Targeting Atp6v1c1 Prevents Inflammation and Bone Erosion Caused by Periodontitis and Reveals Its Critical Function in Osteoimmunology. In PloS one, 10, e0134903. doi:10.1371/journal.pone.0134903. https://pubmed.ncbi.nlm.nih.gov/26274612/

4. Yao, Xijuan, Chen, Hui, Xu, Bing, Ju, Mengyang, Sun, Xinchen. 2020. The ATPase subunit of ATP6V1C1 inhibits autophagy and enhances radiotherapy resistance in esophageal squamous cell carcinoma. In Gene, 768, 145261. doi:10.1016/j.gene.2020.145261. https://pubmed.ncbi.nlm.nih.gov/33183740/

5. Feng, Shengmei, Zhu, Guochun, McConnell, Matthew, Li, Yi-Ping, Chen, Wei. 2013. Silencing of atp6v1c1 prevents breast cancer growth and bone metastasis. In International journal of biological sciences, 9, 853-62. doi:10.7150/ijbs.6030. https://pubmed.ncbi.nlm.nih.gov/24155661/

6. Feng, Shengmei, Deng, Lianfu, Chen, Wei, Xu, Guoliang, Li, Yi-Ping. . Atp6v1c1 is an essential component of the osteoclast proton pump and in F-actin ring formation in osteoclasts. In The Biochemical journal, 417, 195-203. doi:10.1042/BJ20081073. https://pubmed.ncbi.nlm.nih.gov/18657050/