ZIP4 silencing improves bone loss in pancreatic cancer.
ZIP4 silencing improves bone loss in pancreatic cancer.
复制标题
ZIP4 沉默可改善胰腺癌中的骨质流失。
DOI：
10.18632/oncotarget.4667
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发表时间：
2015-09-22
期刊：
影响因子：
--
通讯作者：
Li M
中科院分区：
文献类型：
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作者：
Zhang Q;Sun X;Yang J;Ding H;LeBrun D;Ding K;Houchen CW;Postier RG;Ambrose CG;Li Z;Bi X;Li M
代谢性骨疾病与几种人类癌症相关。胰腺癌患者通常遭受严重的营养缺乏、肌肉萎缩和骨量丢失。我们先前发现，锌转运蛋白ZIP4的沉默可延长生存期并降低体内恶病质的严重程度。然而，ZIP4在胰腺癌相关的骨丢失中的作用仍然未知。在本研究中，我们在原位异种移植小鼠模型中研究了ZIP4敲低对股骨的骨结构、成分和力学性能的影响。我们的数据显示，ZIP4的沉默导致骨组织矿物质密度增加、骨结晶度降低，并通过RANK/RANKL通路恢复骨强度。这些结果进一步支持了ZIP4对胰腺癌进展的影响，并表明其作为治疗此类毁灭性疾病及癌症相关病症患者的治疗靶点的潜在重要性。
Metabolic bone disorders are associated with several types of human cancers. Pancreatic cancer patients usually suffer from severe nutrition deficiency, muscle wasting, and loss of bone mass. We have previously found that silencing of a zinc transporter ZIP4 prolongs the survival and reduces the severity of the cachexia in vivo. However, the role of ZIP4 in the pancreatic cancer related bone loss remains unknown. In this study we investigated the effect of ZIP4 knockdown on the bone structure, composition and mechanical properties of femurs in an orthotopic xenograft mouse model. Our data showed that silencing of ZIP4 resulted in increased bone tissue mineral density, decreased bone crystallinity and restoration of bone strength through the RANK/RANKL pathway. The results further support the impact of ZIP4 on the progression of pancreatic cancer, and suggest its potential significance as a therapeutic target for treating patients with such devastating disease and cancer related disorders.