Zinc and its transporter ZIP10 are involved in invasive behavior of breast cancer cells
Zinc and its transporter ZIP10 are involved in invasive behavior of breast cancer cells
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DOI：
10.1111/j.1349-7006.2007.00446.x
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发表时间：
2007-05-01
期刊：
影响因子：
5.7
通讯作者：
Hirano, Toshio
中科院分区：
文献类型：
--
作者：
Kagara, Naofumi;Tanaka, Natsumi;Hirano, Toshio
锌是维持所有生命的必需元素。缺锌会导致味觉障碍、免疫缺陷、皮肤问题、生长发育和智力迟钝。最近的报告表明，锌与癌症风险增加有关，尽管目前尚不清楚锌或其转运蛋白是否参与癌症进展。在这里，我们表明锌及其转运蛋白ZIP 10参与了乳腺癌细胞的侵袭行为。对临床样本进行ZIP 10 mRNA表达的筛选表明，ZIP 10与乳腺癌淋巴结转移显著相关。此外，ZIP 10 mRNA在侵袭性和转移性乳腺癌细胞系MDA-MB-231和MDA-MB-435 S中的表达高于转移性较低的乳腺癌细胞系，如MCF 7、T47 D、ZR 75 -1和ZR 75 -30。在体外细胞迁移试验中，锌转运蛋白ZIP 10和细胞内锌的耗竭抑制了MDA-MB-231和MDA-MB-435 S细胞的迁移活性。这些结果表明，锌和ZIP 10在高转移性乳腺癌细胞的迁移活性中起着至关重要的作用，并建议ZIP 10作为乳腺癌转移表型的可能标志物和新的治疗策略的有希望的靶点。
Zinc is an essential element, necessary for sustaining all life. Zinc deficiency causes taste impairments, immune deficiency, skin problems, and growth and mental retardation. Recent reports suggest that zinc is associated with an increased risk of cancer, although it is still unclear whether zinc or its transporters are involved in cancer progression. Here we show that zinc and its transporter ZIP10 are involved in the invasive behavior of breast cancer cells. The screening of clinical samples for ZIP10 mRNA expression suggested that ZIP10 was significantly associated with the metastasis of breast cancer to the lymph node. In addition, the expression of ZIP10 mRNA was higher in the invasive and metastatic breast cancer cell lines MDA-MB-231 and MDA-MB-435S than in less metastatic breast cancer cell lines, such as MCF7, T47D, ZR75-1 and ZR75-30. In in vitro cell migration assays, the depletion of zinc transporter ZIP10 and intracellular zinc inhibited the migratory activity of MDA-MB-231 and MDA-MB-435S cells. These results showed that zinc and ZIP10 play an essential role in the migratory activity of highly metastatic breast cancer cells, and suggest ZIP10 as a possible marker for the metastatic phenotype of breast cancer and a promising target of novel treatment strategies.