Huang Bo, Yuan Qihang, Sun Jiaao, Wang Chao, Yang Dong
Liaoning Cancer Hospital & Institute, Shenyang, China.
First Affiliated Hospital of Dalian Medical University, Dalian, China.
Front Immunol. 2025 Apr 15;16:1561560. doi: 10.3389/fimmu.2025.1561560. eCollection 2025.
Thymidine phosphorylase (TYMP), a protein found in both prokaryotic and eukaryotic cells, is encoded by a gene located in the q13 region of chromosome 22. With a relative molecular mass of 55,000, TYMP exists as a homodimer. Recent research has increasingly illuminated the diverse functions of TYMP. It is known to facilitate platelet activation, osteoclast differentiation, and angiogenesis. Mutations in the TYMP gene are linked to mitochondrial neurogastrointestinal encephalomyopathy. Beyond its physiological roles, TYMP contributes significantly to tumor growth and cancer progression, where it promotes angiogenesis, modulates epigenetic genes, inhibits apoptosis, and acts as a critical enzyme in the nucleoside metabolic rescue pathway. Moreover, TYMP holds substantial implications in cancer treatment and prognosis. Given its involvement in cancer progression, TYMP inhibitors may prove valuable in inhibiting tumor growth and metastasis. Interestingly, while TYMP can drive tumor growth, certain concentrations of TYMP also enhance the cytotoxic effects of chemotherapy drugs such as 5-fluorouracil (5-FU). Although challenges exist-such as the potential disruption of normal physiological functions when inhibiting TYMP-the protein remains a promising target for cancer treatment. Ongoing research on TYMP could deepen our understanding of human physiology and the pathogenesis of cancer and open new avenues for therapeutic interventions. This article provides a comprehensive review of TYMP's structure, physiological functions, and its role in tumorigenesis and anti-tumor therapy.
胸苷磷酸化酶（TYMP）是一种存在于原核细胞和真核细胞中的蛋白质，由位于22号染色体q13区域的一个基因编码。TYMP的相对分子质量为55000，以同型二聚体形式存在。最近的研究越来越多地揭示了TYMP的多种功能。已知它有助于血小板活化、破骨细胞分化和血管生成。TYMP基因的突变与线粒体神经胃肠性脑肌病有关。除了其生理作用外，TYMP在肿瘤生长和癌症进展中也起着重要作用，它促进血管生成、调节表观遗传基因、抑制细胞凋亡，并在核苷代谢挽救途径中作为关键酶发挥作用。此外，TYMP在癌症治疗和预后方面具有重要意义。鉴于其参与癌症进展，TYMP抑制剂可能在抑制肿瘤生长和转移方面具有价值。有趣的是，虽然TYMP可以驱动肿瘤生长，但一定浓度的TYMP也会增强化疗药物如5-氟尿嘧啶（5-FU）的细胞毒性作用。尽管存在挑战，如抑制TYMP时可能破坏正常生理功能，但该蛋白仍然是癌症治疗的一个有前景的靶点。对TYMP的持续研究可能会加深我们对人体生理学和癌症发病机制的理解，并为治疗干预开辟新途径。本文对TYMP的结构、生理功能及其在肿瘤发生和抗肿瘤治疗中的作用进行了全面综述。
