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

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机构: [1]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. [2]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. [3]Medical Research Center, The Affiliated Yue Bei People's Hospital, Shantou University Medical College, Shaoguan, 512025, China. [4]Basic Medical Science Department, Zhuhai Campus of Zunyi Medical University, Zhuhai, 519041, China. [5]Oncology Department, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518060, China. [6]Institute of Otorhinolaryngology and Shenzhen Key of Otorhinolaryngology, Longgang Otorhinolaryngology Hospital, Shenzhen, 518172, China. [7]The Bio-bank of Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, 518000, China. [8]Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College, Nanchong, Sichuan, 637199, China.
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关键词: E-cadherin metastasis nasopharyngeal carcinoma (NPC) phosphoglycerate kinase 1 (PGK1) TMEM52B isoforms

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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.© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.

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出版当年[2023]版:
大类 | 1 区 材料科学
小类 | 1 区 化学:综合 1 区 材料科学:综合 2 区 纳米科技
最新[2023]版:
大类 | 1 区 材料科学
小类 | 1 区 化学:综合 1 区 材料科学:综合 2 区 纳米科技
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出版当年[2023]版:
Q1 CHEMISTRY, MULTIDISCIPLINARY Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY Q1 NANOSCIENCE & NANOTECHNOLOGY
最新[2023]版:
Q1 CHEMISTRY, MULTIDISCIPLINARY Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY Q1 NANOSCIENCE & NANOTECHNOLOGY

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第一作者机构: [1]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. [2]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. [3]Medical Research Center, The Affiliated Yue Bei People's Hospital, Shantou University Medical College, Shaoguan, 512025, China.
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通讯机构: [1]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. [3]Medical Research Center, The Affiliated Yue Bei People's Hospital, Shantou University Medical College, Shaoguan, 512025, China. [4]Basic Medical Science Department, Zhuhai Campus of Zunyi Medical University, Zhuhai, 519041, China. [8]Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College, Nanchong, Sichuan, 637199, China.
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