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首页> 外文期刊>Cell cycle >Anosmin-1 involved in neuronal cell migration is hypoxia inducible and cancer regulated.
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Anosmin-1 involved in neuronal cell migration is hypoxia inducible and cancer regulated.

机译：参与神经元细胞迁移的Anosmin-1可诱导缺氧并调节癌症。

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摘要

Functional expression of KAL1 gene is critical in the migration of GnRH neurons from the olfactory placode to the hypothalamus in embryogenesis. This gene thus far has not been shown to play a functional role in any other physiological or pathological process either in the developed brain or in peripheral tissues. We show here that KAL1 gene expression is decreased in early stage and increased in later stages of cancers. Screening of colon, lung and ovarian cancer cDNA panels indicated significant decrease in KAL1 expression in comparison to corresponding uninvolved tissues. However, KAL1 expression increased with the progression of cancer from early (I and II) stages to later (III and IV) stages of the cancer. There was a direct correlation between the TGFbeta and KAL1 expression in colon cancer cDNA. Using colon cancer cell lines, we showed that TGFbeta induces KAL1 gene expression and secretion of anosmin-1 protein (KAL1 coded protein). We further report that hypoxia induces anosmin-1 expression; anosmin-1 protects cancer cells from apoptosis activated by hypoxia and increases cancer cell mobility. Using siRNA technique we found that KAL1 expression following hypoxia is hypoxia-inducible factor (HIF-1)alpha dependent. Our results suggest that KAL1 gene expression plays an important role in cancer metastasis and protection from apoptosis.
机译：KAL1基因的功能性表达在胚胎发生中GnRH神经元从嗅觉平台到下丘脑的迁移中至关重要。迄今为止，尚未证明该基因在发育中的大脑或外周组织中的任何其他生理或病理过程中起功能性作用。我们在这里显示，KAL1基因表达在癌症的早期减少，在癌症的后期增加。结肠癌，肺癌和卵巢癌cDNA面板的筛选显示，与相应的未累及组织相比，KAL1表达显着降低。然而，随着癌症从癌症的早期（I和II）阶段发展到晚期（III和IV）阶段，KAL1表达增加。 TGFbeta和KAL1在结肠癌cDNA中的表达直接相关。使用结肠癌细胞系，我们表明TGFbeta诱导KAL1基因表达和anosmin-1蛋白（KAL1编码蛋白）的分泌。我们进一步报告缺氧诱导anosmin-1表达。 anosmin-1保护癌细胞免受缺氧激活的细胞凋亡，并增加癌细胞的移动性。使用siRNA技术，我们发现缺氧后KAL1表达是缺氧诱导因子（HIF-1）α依赖性的。我们的结果表明，KAL1基因表达在癌症转移和防止细胞凋亡中起着重要作用。

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