Zinc transporter SLC39A13/ZIP13 facilitates the metastasis of human ovarian cancer cells via activating Src/FAK signaling pathway.
Zinc transporter SLC39A13/ZIP13 facilitates the metastasis of human ovarian cancer cells via activating Src/FAK signaling pathway.
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锌转运蛋白SLC39A13/ZIP13通过激活Src/FAK信号通路促进人卵巢癌细胞的转移
DOI：
10.1186/s13046-021-01999-3
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发表时间：
2021-06-21
期刊：
影响因子：
--
通讯作者：
Xu Z
中科院分区：
文献类型：
--
作者：
Cheng X;Wang J;Liu C;Jiang T;Yang N;Liu D;Zhao H;Xu Z
研究背景锌转运蛋白与包括癌症在内的多种人类疾病的发病机制有关。卵巢癌是妇科最致命的恶性肿瘤，其特点是进展迅速，转移广泛。然而，锌转运蛋白在卵巢癌转移中的功能和潜在机制尚不清楚。方法采用Kaplan-Meier方法评估锌转运蛋白基因表达与卵巢癌临床预后的关系。 http://kmplot.com/analysis/ ).进行免疫组织化学以研究ZIP 13的预后重要性。耗尽卵巢癌细胞系中ZIP 13的表达以探索其在体外和体内测定中对增殖、粘附、迁移和侵袭的影响。通过RNA-Seq、定量RT-PCR和Western blot分析，探讨ZIP 13调控的下游靶基因。结果几种锌转运蛋白的表达与卵巢癌患者的临床预后高度相关。其中，ZIP 13高表达是卵巢癌患者生存不良的独立预后因素。ZIP 13基因敲除在体内外均能抑制卵巢癌细胞的恶性表型。进一步的研究表明ZIP 13调节细胞内锌的分布，进而影响细胞外基质组织和甜菜碱介导的信号通路相关基因的表达。结论ZIP 13通过调控Src/FAK信号通路，可能成为卵巢癌转移的新驱动因子，有望成为卵巢癌预后评估和靶向治疗的生物标志物。
BackgroundZinc transporters have been found to be associated with the pathogenesis of numerous human diseases including cancer. As the most lethal gynecologic malignancy, ovarian cancer is characterized by rapid progression and widespread metastases. However, the function and underlying mechanism of zinc transporters in ovarian cancer metastasis remain unclear.MethodsThe relationship between zinc transporter gene expressions and clinical outcomes of ovarian cancer was assessed with the online database Kaplan-Meier plotter ( http://kmplot.com/analysis/ ). Immunohistochemistry was performed to investigate the prognostic importance of ZIP13. The expression of ZIP13 in ovarian cancer cell lines was depleted to explore its effect on proliferation, adhesion, migration, and invasion both in vitro and in vivo assays. RNA-Seq, quantitative RT-PCR, and western blot analysis were performed to explore ZIP13-regulated downstream target genes.ResultsThe expressions of several zinc transporters were highly associated the clinical outcomes of ovarian cancer patients. Among them, high ZIP13 expression was an independent prognostic factor for poor survival in patients with ovarian cancer. ZIP13 knockout suppressed the malignant phenotypes of ovarian cancer cells both in vitro and in vivo. Further investigation revealed that ZIP13 regulated intracellular zinc distribution and then affected the expressions of genes involved in extracellular matrix organization and cytokine-mediated signaling pathway. This led to the activation of Src/FAK pathway with increased expressions of pro-metastatic genes but decreased expressions of tumor suppressor genes.ConclusionsZIP13 is shown to be a novel driver of metastatic progression by modulating the Src/FAK signaling pathway, which may serve as a promising biomarker for prognostic evaluation and targeted therapy in ovarian cancer.
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影响因子：
12.4
作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
3.7
作者：
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通讯作者：
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