Up-regulation of neogenin-1 increases cell proliferation and motility in gastric cancer.
Up-regulation of neogenin-1 increases cell proliferation and motility in gastric cancer.
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DOI：
10.18632/oncotarget.1960
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发表时间：
2014-05-30
期刊：
影响因子：
--
通讯作者：
Chun KH
中科院分区：
文献类型：
--
作者：
Kim SJ;Wang YG;Lee HW;Kang HG;La SH;Choi IJ;Irimura T;Ro JY;Bresalier RS;Chun KH
尽管在人胃癌组织中检测到再生蛋白-1的高表达，但由于缺乏再生蛋白-1在癌症中的研究，其在胃肿瘤发生中的作用仍不清楚。因此，我们在此阐述了再生蛋白-1在胃癌中的作用及其调控机制。再生蛋白-1消融降低胃癌细胞的增殖和迁移，而其过度表达逆转了这些作用。使用胃癌细胞的异种移植分析显示再生蛋白-1耗尽对肿瘤生长的统计学显著抑制。有趣的是，galectin-3与HSF-1直接相互作用，促进了neogenin-1启动子的核定位和结合，从而驱动其转录和胃癌细胞运动。半乳糖凝集素-3增加的胃癌细胞运动性被HSF-1耗竭下调。此外，在胃癌患者的恶性组织中检测到galectin-3和neogenin-1以及HSF-1和neogenin-1的平行表达模式。总之，再生蛋白-1的高表达促进胃癌的增殖和运动，并且其表达受HSF-1和半乳糖凝集素-3相互作用的调节。此外，我们建议进一步研究再生蛋白-1及其相关通路，为胃癌治疗提供合适的靶点。
Although elevated expression of neogenin-1 has been detected in human gastric cancer tissue, its role in gastric tumorigenesis remains unclear due to the lack of neogenin-1 studies in cancer. Therefore, we demonstrated here the function and regulatory mechanism of neogenin-1 in gastric cancer. Neogenin-1 ablation decreased proliferation and migration of gastric cancer cells, whereas its over-expression reversed these effects. Xenografted analyses using gastric cancer cells displayed statistically significant inhibition of tumor growth by neogenin-1 depletion. Interestingly, galectin-3 interacted with HSF-1 directly, which facilitated nuclear-localization and binding on neogenin-1 promoter to drive its transcription and gastric cancer cell motility. The galectin-3-increased gastric cancer cell motility was down-regulated by HSF-1 depletion. Moreover, the parallel expression patterns of galectin-3 and neogenin-1, as well as those of HSF-1 and neogenin-1, were detected in the malignant tissues of gastric cancer patients. Taken together, high-expression of neogenin-1 promotes gastric cancer proliferation and motility and its expression is regulated by HSF-1 and galectin-3 interaction. In addition, we propose further studies for neogenin-1 and its associated pathways to provide them as a proper target for gastric cancer therapy.
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