锌转运蛋白ZIP13在卵巢癌转移中的作用机制研究

Invasion and metastasis are responsible for the high mortality in patients with ovarian cancer. However, little is known about the detailed molecular mechanisms underlying the invasion and metastasis of ovarian cancer, which has become a major bottleneck hindering the advancement of ovarian cancer clinical research. Our previous study found that zinc transporter ZIP13 is associated with poor survival of ovarian cancer patients, and can be used as a promising biomarker to assess clinical prognosis. Further study revealed that ZIP13 can regulate the expression of epithelial-to-mesenchymal transition (EMT)-related marker molecules. However, the mechanism by which ZIP13 affects the invasion and metastasis of ovarian cancer, especially the regulation of specific EMT process remains to be elucidated in detail. In this project, a variety of techniques such as biochemistry, molecular biology, proteomics, bioinformatics and clinical oncology, will be performed to explore the biological functions and molecular networks of ZIP13 in the invasion and metastasis of ovarian cancer at different perspectives from molecular, cellular, animal models, and clinical tumor samples. The molecular mechanisms of ZIP13 in the invasion and metastasis of ovarian cancer will be expounded. In conclusion, these results might identify new tumor biomarkers and candidate drug targets for clinical prognostic evaluation and treatment of ovarian cancer, and will contribute to the in-depth understanding of the progression of ovarian cancer, thereby providing new knowledge for the invasion and metastasis theory of ovarian cancer.

侵袭和转移是造成卵巢癌高死亡率的主要原因。然而卵巢癌发生侵袭转移的具体分子机制仍未完全阐明，已经成为阻碍卵巢癌临床研究取得突破性进展的主要瓶颈。我们前期研究发现锌转运蛋白ZIP13与卵巢癌患者的生存密切相关，可作为评估临床预后的潜在分子标志物。并且进一步研究发现ZIP13能够调控EMT相关标志分子的表达，但其如何影响卵巢癌侵袭转移，尤其是调控EMT过程中的具体作用机制仍有待详细研究。本项目利用生物化学、分子生物学、蛋白质组学、生物信息学和临床肿瘤学等多种技术手段，从分子、细胞、动物模型和临床肿瘤样本等不同层次研究ZIP13在卵巢癌侵袭转移中的生物学功能以及相应的分子调控网络，并阐明其在卵巢癌侵袭转移中的具体作用机制。相关研究不仅有助于为卵巢癌临床预后评估和治疗提供新的肿瘤标志物和候选药物靶标，也将有助于更深入地理解卵巢癌转移进展过程，从而为完善现有卵巢癌侵袭转移理论体系提供新知识。

侵袭和转移是造成卵巢癌高死亡率的主要原因，然而卵巢癌发生侵袭转移的具体分子机制仍未完全阐明。锌转运蛋白表达异常与多种肿瘤的发生发展密切相关。然而目前其在卵巢癌中的作用及机制尚未研究。本项目通过对锌转运蛋白家族成员与卵巢癌患者预后分析，发现ZIP13与卵巢癌患者的生存密切相关，可作为评估临床预后的潜在分子标志物。通过细胞实验和动物实验研究发现，ZIP13敲除降低卵巢癌细胞的恶性表型，如细胞增殖、侵袭和转移。进一步研究表明ZIP13通过调控胞内锌离子的分布，激活Src/FAK途径，从而影响转移相关基因的表达，最终促进卵巢癌转移。相关研究不仅有助于为卵巢癌临床预后评估和治疗提供新的肿瘤标志物和候选药物靶标，也将有助于更深入地理解卵巢癌转移进展过程，从而为完善现有卵巢癌侵袭转移理论体系提供新知识。