Mitochondrial outer membrane protein MTUS1/ATIP1 exerts antitumor effects through ROS-induced mitochondrial pyroptosis in head and neck squamous cell carcinoma

Tang, Dongxiao; Zhao, Luodan; Huang, Shuojin; Li, Wuguo; He, Qianting; Wang, Anxun

doi:10.7150/ijbs.94795

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International Journal of Medical Sciences

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Int J Biol Sci 2024; 20(7):2576-2591. doi:10.7150/ijbs.94795 This issue Cite

Research Paper

Mitochondrial outer membrane protein MTUS1/ATIP1 exerts antitumor effects through ROS-induced mitochondrial pyroptosis in head and neck squamous cell carcinoma

Dongxiao Tang^1,2†, Luodan Zhao^3†, Shuojin Huang¹, Wuguo Li⁴, Qianting He^1✉, Anxun Wang^1✉

1. Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China.
2. Department of Stomatology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510630, China.
3. Department of Stomatology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, China.
4. Animal Experiment Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China.
^†These authors contributed equally to this work.

Citation:

Tang D, Zhao L, Huang S, Li W, He Q, Wang A. Mitochondrial outer membrane protein MTUS1/ATIP1 exerts antitumor effects through ROS-induced mitochondrial pyroptosis in head and neck squamous cell carcinoma. Int J Biol Sci 2024; 20(7):2576-2591. doi:10.7150/ijbs.94795. https://www.ijbs.com/v20p2576.htm

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Abstract

We showed that microtubule-associated tumor suppressor gene (MTUS1/ATIP) downregulation correlated with poor survival in head and neck squamous cell carcinoma (HNSCC) patients and that MTUS1/ATIP1 was the most abundant isoform in HNSCC tissue. However, the location and function of MTUS1/ATIP1 have remain unclear. In this study, we confirmed that MTUS1/ATIP1 inhibited proliferation, growth and metastasis in HNSCC in cell- and patient-derived xenograft models in vitro and in vivo. MTUS1/ATIP1 localized in the outer mitochondrial membrane, influence the morphology, movement and metabolism of mitochondria and stimulated oxidative stress in HNSCC cells by directly interacting with MFN2. MTUS1/ATIP1 activated ROS, recruiting Bax to mitochondria, facilitating cytochrome c release to the cytosol to activate caspase-3, and inducing GSDME-dependent pyroptotic death in HNSCC cells. Our findings showed that MTUS1/ATIP1 localized in the outer mitochondrial membrane in HNSCC cells and mediated anticancer effects through ROS-induced pyroptosis, which may provide a novel therapeutic strategy for HNSCC treatment.

Keywords: MTUS1/ATIP1, mitochondria, HNSCC, ROS, pyroptosis

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APA

Tang, D., Zhao, L., Huang, S., Li, W., He, Q., Wang, A. (2024). Mitochondrial outer membrane protein MTUS1/ATIP1 exerts antitumor effects through ROS-induced mitochondrial pyroptosis in head and neck squamous cell carcinoma. International Journal of Biological Sciences, 20(7), 2576-2591. https://doi.org/10.7150/ijbs.94795.

ACS

Tang, D.; Zhao, L.; Huang, S.; Li, W.; He, Q.; Wang, A. Mitochondrial outer membrane protein MTUS1/ATIP1 exerts antitumor effects through ROS-induced mitochondrial pyroptosis in head and neck squamous cell carcinoma. Int. J. Biol. Sci. 2024, 20 (7), 2576-2591. DOI: 10.7150/ijbs.94795.

NLM

CSE

Tang D, Zhao L, Huang S, Li W, He Q, Wang A. 2024. Mitochondrial outer membrane protein MTUS1/ATIP1 exerts antitumor effects through ROS-induced mitochondrial pyroptosis in head and neck squamous cell carcinoma. Int J Biol Sci. 20(7):2576-2591.

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