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首页> 外文期刊>Cancer Cell >Hypoxia promotes invasive growth by transcriptional activation of the met protooncogene.
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Hypoxia promotes invasive growth by transcriptional activation of the met protooncogene.

机译:缺氧通过met原癌基因的转录激活促进侵袭性生长。

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摘要

Hypoxia unleashes the invasive and metastatic potential of tumor cells by largely unknown mechanisms. The Met tyrosine kinase, a high affinity receptor for hepatocyte growth factor (HGF), plays a crucial role in controlling invasive growth and is often overexpressed in cancer. Here we show that: (1) hypoxia activates transcription of the met protooncogene, resulting in higher levels of Met; (2) hypoxic areas of tumors overexpress Met; (3) hypoxia amplifies HGF signaling; (4) hypoxia synergizes with HGF in inducing invasion; (5) the proinvasive effects of hypoxia are mimicked by Met overexpression; and (6) inhibition of Met expression prevents hypoxia-induced invasive growth. These data show that hypoxia promotes tumor invasion by sensitizing cells to HGF stimulation, providing a molecular basis to explain Met overexpression in cancer.
机译:缺氧通过很大程度上未知的机制释放了肿瘤细胞的侵袭和转移潜能。 Met酪氨酸激酶是肝细胞生长因子(HGF)的高亲和力受体,在控制侵袭性生长中起关键作用,并且通常在癌症中过表达。在这里,我们表明:(1)缺氧激活了原癌基因的转录,导致更高的Met水平; (2)肿瘤低氧区过表达Met; (3)缺氧会放大HGF信号; (4)低氧与HGF协同诱导侵袭; (5)Met过表达可模仿缺氧的侵袭性作用; (6)抑制Met表达可防止缺氧诱导的侵袭性生长。这些数据表明,低氧通过使细胞对HGF刺激敏感来促进肿瘤侵袭,为解释Met在癌症中的过度表达提供了分子基础。

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