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锌转运蛋白ZIP4的分子结构、功能及其在肿瘤治疗中的应用研究进展

Research progress on the molecular structure, function, and application in tumor therapy of zinc transporter ZIP4.

作者信息

Guo Haijun, Wang Shaohua, Zhang Hui, Li Jie, Wang Chao, Liu Zhikun, Chen Jun, Wang Kai, Wei Xuyong, Wei Qiang, Xu Xiao

机构信息

Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China.

Zhejiang University School of Medicine, Hangzhou, 310058, China.

出版信息

Int J Biol Sci. 2024 Nov 4;20(15):5910-5924. doi: 10.7150/ijbs.102460. eCollection 2024.

Abstract

ZIP4, a pivotal member of the ZIP family, is the causative gene for the hereditary disorder AE (acrodermatitis enteropathica) in humans, and plays an essential role in regulating zinc ion balance within cells. While research on the molecular structure of ZIP4 continues, there remains a lack of full understanding regarding the stereo-structural conformation of ZIP4 molecules. Currently, there are two hypotheses concerning the transport of zinc ions into the cytoplasm by ZIP4, with some contradictions between experimental studies. Recent investigations have revealed that ZIP4 is involved in tumor growth, metastasis, drug tolerance, and various other processes. Most studies suggest that ZIP4 regulates the malignant biological behavior of tumors through zinc ions as a second messenger: however, latest research has identified that ZIP4 itself binds to Ephrin-B1 to regulate tumor metastasis. This review provides a comprehensive summary of the molecular structure of ZIP4 and its mechanism for transporting zinc ions while also exploring mutual regulation between zinc ions and ZIP4. Furthermore, it summarizes recent research progress on the role of ZIP4 in tumors and discusses its potential as a target for anticancer therapy based on an extensive analysis of research findings. These insights can guide future investigations into the role of ZIP4 in tumors.

摘要

ZIP4是锌转运蛋白(ZIP)家族的关键成员,是人类遗传性疾病肠病性肢端皮炎(AE)的致病基因,在调节细胞内锌离子平衡方面发挥着重要作用。虽然对ZIP4分子结构的研究仍在继续,但对ZIP4分子的立体结构构象仍缺乏全面了解。目前,关于ZIP4将锌离子转运到细胞质中有两种假说,实验研究之间存在一些矛盾。最近的研究表明,ZIP4参与肿瘤生长、转移、耐药性及其他多种过程。大多数研究认为,ZIP4通过锌离子作为第二信使来调节肿瘤的恶性生物学行为;然而,最新研究发现ZIP4本身与Ephrin-B1结合以调节肿瘤转移。本综述全面总结了ZIP4的分子结构及其转运锌离子的机制,同时探讨了锌离子与ZIP4之间的相互调节。此外,基于对研究结果的广泛分析,总结了ZIP4在肿瘤中作用的最新研究进展,并讨论了其作为抗癌治疗靶点的潜力。这些见解可为未来对ZIP4在肿瘤中作用的研究提供指导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30be/11628325/c7a4b6568cd0/ijbsv20p5910g001.jpg

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