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.
摘要：
跨膜蛋白52B(TMEM52B),一个新发现的肿瘤相关基因，据报道可以调节各种肿瘤，然而，其在鼻咽癌（NPC）中的作用尚不清楚。NPC细胞系的转录组学分析显示TMEM52B的频繁过表达，免疫组织化学结果显示TMEM52B与晚期肿瘤分期有关,复发,减少了生存时间。消耗TMEM52B抑制增殖，迁移,入侵,和体内NPC细胞的肿瘤发生。TMEM52B编码两种同工型，TMEM52B-P18和TMEM52B-P20的N端不同。虽然两种亚型表现出相似的致癌作用，并有助于NPC的耐药性，TMEM52B-P20差异促进转移。这种功能差异可能归因于它们不同的亚细胞定位；TMEM52B-P18局限于细胞质，而TMEM52B-P20同时存在于细胞膜和细胞质中。机械上,细胞质TMEM52B通过与磷酸甘油酸激酶1（PGK1）相互作用增强AKT磷酸化，促进NPC生长和转移。同时,膜定位的TMEM52B-P20通过促进其与E3泛素连接酶NEDD4的相互作用来促进E-cadherin的泛素化和降解，从而进一步驱动NPC转移。总之,TMEM52B-P18和TMEM52B-P20亚型通过不同的机制促进NPC细胞的转移。靶向这些TMEM52B亚型的药物可以为具有不同程度转移的癌症患者提供治疗益处。
