Int J Biol Sci 2022; 18(8):3544-3561. doi:10.7150/ijbs.72296 This issue Cite

Research Paper

Cold atmospheric plasmas target breast cancer stemness via modulating AQP3-19Y mediated AQP3-5K and FOXO1 K48-ubiquitination

Xiaofeng Dai1,10✉, Dongyan Cai2✉, Peiyu Wang3,4,5, Nan Nan1, Lihui Yu1, Zhifa Zhang1, Renwu Zhou6, Dong Hua1,2,7, Jianying Zhang8, Kostya (Ken) Ostrikov4,9, Erik Thompson4,5,6

1. Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China.
2. Affiliated Hospital of Jiangnan University, Wuxi 214122, China.
3. Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane 4059, Australia.
4. Translational Research Institute, Woolloongabba, Queensland 4102, Australia.
5. School of Biomedical Sciences, Queensland University of Technology, Brisbane 4059, Australia.
6. School of Chemical and Biomolecular Engineering, University of Sydney, NSW 2006, Australia.
7. Wuxi People's Hospital, Wuxi, 214023, China.
8. BGI College & Henan Institute of Medical and Pharmaceutical Sciences in Academy of Medical Science, Zhengzhou University, 450052, China.
9. School of Chemistry and Physics, Queensland University of Technology, Brisbane, Queensland 4000, Australia.
10. CAPsoul Medical Biotechnology Company, Ltd, Beijing, 100000, China.

Citation:
Dai X, Cai D, Wang P, Nan N, Yu L, Zhang Z, Zhou R, Hua D, Zhang J, Ostrikov KK, Thompson E. Cold atmospheric plasmas target breast cancer stemness via modulating AQP3-19Y mediated AQP3-5K and FOXO1 K48-ubiquitination. Int J Biol Sci 2022; 18(8):3544-3561. doi:10.7150/ijbs.72296. https://www.ijbs.com/v18p3544.htm
Other styles

File import instruction

Abstract

Graphic abstract

Cold atmospheric plasma (CAP) is selective against many cancers with little side effect, yet its molecular mechanism remains unclear. Through whole transcriptome sequencing followed by assays in vitro, in vivo and using clinical samples, we propose CAP as a promising onco-therapy targeting cancer stemness via the AQP3/FOXO1 axis. CAP-generated reactive species penetrated cells via AQP3 and suppressed RPS6KA3, a shared kinase of AQP3 and FOXO1. Reduced AQP3-19Y phosphorylation suppressed SCAF11-mediated AQP3-5K K48-ubiquitination that led to sabotaged FOXO1 stability. Inhibited FOXO1 phosphorylation retarded its regulatory activities in maintaining cancer stemness including ALDH1 and IL6. Enhanced anti-cancer efficacy was observed through combining CAP with Atorvastatin in vitro and in vivo. We propose CAP as a 'selective' onco-therapeutic against cancer stemness, with the AQP3/FOXO1 axis being one molecular mechanism. We report SCAF11 as an E3 ubiquitin ligase of both AQP3 and FOXO1, identify AQP3-5K as an AQP3 K48-ubiquitination site, and emphasize the essential role of AQP3-19Y in this process. We reposition Atorvastatin into the onco-therapeutic portfolio by synergizing it with CAP towards enhanced efficacy. We anticipate the efficacy of CAP in targeting malignancies of high stemness alone or as an adjuvant therapy towards the hope of ultimate cancer cure.

Keywords: Cold atmospheric plasma, cancer stemness, selective onco-therapy, AQP3, FOXO1, SCAF11, ubiquitination, Atorvastatin


Citation styles

APA
Dai, X., Cai, D., Wang, P., Nan, N., Yu, L., Zhang, Z., Zhou, R., Hua, D., Zhang, J., Ostrikov, K.K., Thompson, E. (2022). Cold atmospheric plasmas target breast cancer stemness via modulating AQP3-19Y mediated AQP3-5K and FOXO1 K48-ubiquitination. International Journal of Biological Sciences, 18(8), 3544-3561. https://doi.org/10.7150/ijbs.72296.

ACS
Dai, X.; Cai, D.; Wang, P.; Nan, N.; Yu, L.; Zhang, Z.; Zhou, R.; Hua, D.; Zhang, J.; Ostrikov, K.K.; Thompson, E. Cold atmospheric plasmas target breast cancer stemness via modulating AQP3-19Y mediated AQP3-5K and FOXO1 K48-ubiquitination. Int. J. Biol. Sci. 2022, 18 (8), 3544-3561. DOI: 10.7150/ijbs.72296.

NLM
Dai X, Cai D, Wang P, Nan N, Yu L, Zhang Z, Zhou R, Hua D, Zhang J, Ostrikov KK, Thompson E. Cold atmospheric plasmas target breast cancer stemness via modulating AQP3-19Y mediated AQP3-5K and FOXO1 K48-ubiquitination. Int J Biol Sci 2022; 18(8):3544-3561. doi:10.7150/ijbs.72296. https://www.ijbs.com/v18p3544.htm

CSE
Dai X, Cai D, Wang P, Nan N, Yu L, Zhang Z, Zhou R, Hua D, Zhang J, Ostrikov KK, Thompson E. 2022. Cold atmospheric plasmas target breast cancer stemness via modulating AQP3-19Y mediated AQP3-5K and FOXO1 K48-ubiquitination. Int J Biol Sci. 18(8):3544-3561.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Popup Image