J Cancer 2019; 10(13):2942-2952. doi:10.7150/jca.31055

Research Paper

Sorting Nexin 5 Controls Head and Neck Squamous Cell Carcinoma Progression by Modulating FBW7

Jinyang Cai1, Ming Sun1, Bin Hu2, Brad Windle1, Xin Ge3, Guoping Li4, Yue Sun1✉

1. Philips Institute for Oral Health Research, School of Dentistry and Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA
2. Cancer Mouse Models Developing Shared Resource Core, Virginia Commonwealth University, Richmond, VA 23298, USA
3. Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital of Tongji University, Shanghai, China
4. The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, China

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Citation:
Cai J, Sun M, Hu B, Windle B, Ge X, Li G, Sun Y. Sorting Nexin 5 Controls Head and Neck Squamous Cell Carcinoma Progression by Modulating FBW7. J Cancer 2019; 10(13):2942-2952. doi:10.7150/jca.31055. Available from http://www.jcancer.org/v10p2942.htm

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Abstract

Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent cancer worldwide. Long-term survival rates in patients with HNSCC have not increased significantly in the past 30 years. Therefore, looking for novel molecular targets that control HNSCC progression is urgently required to improve the treatment of HNSCC. Here, we identified Sorting Nexin 5 (SNX5) as a new regulator that plays an oncogenic function in HNSCC progression. Analyzing HNSCC patients' data from the Cancer Genome Atlas (TCGA) indicates that the expression levels of SNX5 in HNSCC are significantly elevated compared to normal tissues. Furthermore, higher SNX5 expression correlates with a worse prognosis for HNSCC patients. These results suggest that SNX5 has an oncogenic role. Consistently, loss of SNX5 in HNSCC cells dramatically reduces colony formation and significantly decreases tumor growth in xenograft mouse models. SNX5 interacts with the tumor suppressor F-box/WD repeat-containing protein 7 (FBW7), an E3 ubiquitin ligase that mediates ubiquitination and degradation of oncoproteins such as c-Myc, NOTCH1, and Cyclin E1. By interacting with FBW7, SNX5 inhibits FBW7-mediated oncoproteins ubiquitination. In this way, SNX5 decreases the FBW7-mediated oncoproteins degradation to promote HNSCC progression.

Keywords: SNX5, HNSCC, FBW7, ubiquitination, oncoprotein