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journal article·2024-09Open access

TMEM52B Isoforms P18 and P20 Differentially Promote the Oncogenesis and Metastasis of Nasopharyngeal Carcinoma

Yuqi Zhu, Yanxin Lu, Chunhua Xu, Yuqian Huang, Ziyi Yu, Tongyu Wang, Longyi Mao, Ximian Liao, Shi Li, Wanqing Zhang, Feng Zhou, Kaiqing Liu, Yu Zhang, Wei Yang, Shasha Min, Yaqin Deng, Zaixing Wang, Xiaoqin Fan, Guohui Nie, Xina Xie, Zesong Li

Advanced Science· Volume 11· Issue 33
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Abstract

Abstract Transmembrane protein 52B (TMEM52B), a newly identified tumor‐related gene, has been reported to regulate various tumors, yet its role in nasopharyngeal carcinoma (NPC) remains unclear. Transcriptomic analysis of NPC cell lines reveals frequent overexpression of TMEM52B, and immunohistochemical results show that TMEM52B is associated with advanced tumor stage, recurrence, and decreased survival time. Depleting TMEM52B inhibits the proliferation, migration, invasion, and oncogenesis of NPC cells in vivo. TMEM52B encodes two isoforms, TMEM52B‐P18 and TMEM52B‐P20, differing in their N‐terminals. While both isoforms exhibit similar pro‐oncogenic roles and contribute to drug resistance in NPC, TMEM52B‐P20 differentially promotes metastasis. This functional discrepancy may be attributed to their distinct subcellular localization; TMEM52B‐P18 is confined to the cytoplasm, while TMEM52B‐P20 is found both at the cell membrane and in the cytoplasm. Mechanistically, cytoplasmic TMEM52B enhances AKT phosphorylation by interacting with phosphoglycerate kinase 1 (PGK1), fostering NPC growth and metastasis. Meanwhile, membrane‐localized TMEM52B‐P20 promotes E‐cadherin ubiquitination and degradation by facilitating its interaction with the E3 ubiquitin ligase NEDD4, further driving NPC metastasis. In conclusion, the TMEM52B‐P18 and TMEM52B‐P20 isoforms promote the metastasis of NPC cells through different mechanisms. Drugs targeting these TMEM52B isoforms may offer therapeutic benefits to cancer patients with varying degrees of metastasis.
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Research context

OpenAlex topics: Cancer-related gene regulation · RNA modifications and cancer · Ubiquitin and proteasome pathways

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Guangdong Provincial Key Laboratory of Systems Biology and Synthetic Biology for Urogenital Tumors Shenzhen Key Laboratory of Genitourinary Tumor Department of Urology Shenzhen Institute of Translational Medicine The First Affiliated Hospital of Shenzhen University Shenzhen Second People's Hospital Shenzhen 518000 China

Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging National‐Regional Key Technology Engineering Laboratory for Medical Ultrasound School of Biomedical Engineering Shenzhen University Medical School Shenzhen 518060 China

Medical Research Center The Affiliated Yue Bei People's Hospital Shantou University Medical College Shaoguan 512025 China

Basic Medical Science Department Zhuhai Campus of Zunyi Medical University Zhuhai 519041 China

Oncology Department The Eighth Affiliated Hospital Sun Yat‐sen University Shenzhen 518060 China

Institute of Otorhinolaryngology and Shenzhen Key of Otorhinolaryngology Longgang Otorhinolaryngology Hospital Shenzhen 518172 China

The Bio‐bank of Shenzhen Second People's Hospital The First Affiliated Hospital of Shenzhen University Shenzhen Guangdong 518000 China

Institute of Basic Medicine and Forensic Medicine North Sichuan Medical College Nanchong Sichuan 637199 China

Funding

National Natural Science Foundation of China · Natural Science Foundation of Guangdong Province · Science, Technology and Innovation Commission of Shenzhen Municipality

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