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J Cancer 2024; 15(4):1124-1137. doi:10.7150/jca.91360 This issue Cite

Research Paper

AQP3 Promotes the Invasion and Metastasis in Cervical Cancer by Regulating NOX4-derived H2O2 Activation of Syk/PI3K/Akt Signaling Axis

Qixin Wang1#, Bingjie Lin1#, Hongjian Wei1, Xin Wang1, Xiaojing Nie1,2, Yonghua Shi1,2✉

1. Department of Pathology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, Xinjiang 830017, China.
2. Xinjiang Key Laboratory of Molecular Biology for Endemic Diseases, Xinjiang Medical University, Urumqi, Xinjiang 830017, China.
# Co-authors, they have equal contributions to this paper.

✉ Corresponding author: Yonghua Shi, Ph. D., M.D. Email: shiyonghuaedu.cn; Tel.: 86-991-2110119.

Citation:
Wang Q, Lin B, Wei H, Wang X, Nie X, Shi Y. AQP3 Promotes the Invasion and Metastasis in Cervical Cancer by Regulating NOX4-derived H2O2 Activation of Syk/PI3K/Akt Signaling Axis. J Cancer 2024; 15(4):1124-1137. doi:10.7150/jca.91360. https://www.jcancer.org/v15p1124.htm
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Abstract

Graphic abstract

Unrestrained chronic inflammation leads to the abnormal activity of NOX4 and the subsequent production of excessive hydrogen peroxide (H2O2). Excessive H2O2 signaling triggered by prolonged inflammation is thought to be one of the important reasons for the progression of some types of cancer including cervical cancer. Aquaporin 3 (AQP3) is a member of the water channel protein family, and it remains unknown whether AQP3 can regulate the transmembrane transport of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4)-derived H2O2 induced by the stimulation of inflammatory factors to facilitate the malignant progression in cervical cancer. In this study, cervical cancer HeLa cell line was respectively treated with diphenyleneiodonium (DPI), N-Acetylcysteine (NAC) or lentivirus-shRNA- AQP3. Plate cloning, cell migration or transwell invasion assays, etc. were performed to detect the invasive and migration ability of the cells. Western blot and CO-IP were used to analyze the mechanism of AQP3 regulating H2O2 conduction. Finally, in vivo assays were performed for validation in nude mice. AQP3 Knockdown, DPI or NAC treatments all reduced intracellular H2O2 influx, and the activation of Syk/PI3K/Akt signal axis was inhibited, the migration and invasive ability of the cells was attenuated. In vivo assays confirmed that the excessive H2O2 transport through AQP3 enhanced the infiltration and metastasis of cervical cancer. These results suggest that AQP3 activates H2O2/Syk/PI3K/Akt signaling axis through regulating NOX4-derived H2O2 transport to contribute to the progression of cervical cancer, and AQP3 may be a potential target for the clinical treatment of advanced cervical cancer.

Keywords: AQP3, H2O2, Syk, Akt, Cervical cancer

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APA
Wang, Q., Lin, B., Wei, H., Wang, X., Nie, X., Shi, Y. (2024). AQP3 Promotes the Invasion and Metastasis in Cervical Cancer by Regulating NOX4-derived H2O2 Activation of Syk/PI3K/Akt Signaling Axis. Journal of Cancer, 15(4), 1124-1137. https://doi.org/10.7150/jca.91360.

ACS
Wang, Q.; Lin, B.; Wei, H.; Wang, X.; Nie, X.; Shi, Y. AQP3 Promotes the Invasion and Metastasis in Cervical Cancer by Regulating NOX4-derived H2O2 Activation of Syk/PI3K/Akt Signaling Axis. J. Cancer 2024, 15 (4), 1124-1137. DOI: 10.7150/jca.91360.

NLM
Wang Q, Lin B, Wei H, Wang X, Nie X, Shi Y. AQP3 Promotes the Invasion and Metastasis in Cervical Cancer by Regulating NOX4-derived H2O2 Activation of Syk/PI3K/Akt Signaling Axis. J Cancer 2024; 15(4):1124-1137. doi:10.7150/jca.91360. https://www.jcancer.org/v15p1124.htm

CSE
Wang Q, Lin B, Wei H, Wang X, Nie X, Shi Y. 2024. AQP3 Promotes the Invasion and Metastasis in Cervical Cancer by Regulating NOX4-derived H2O2 Activation of Syk/PI3K/Akt Signaling Axis. J Cancer. 15(4):1124-1137.

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