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首页> 外文期刊>Cell cycle >Surviving without oxygen: hypoxia regulation of mammary morphogenesis and anoikis.
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Surviving without oxygen: hypoxia regulation of mammary morphogenesis and anoikis.

机译:在没有氧气的情况下生存:缺氧调节了乳腺形态发生和无神经。

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Tumor hypoxia correlates with resistance to chemotherapy, increased incidence of metastasis and poor clinical prognosis. Early breast cancer lesions, such as carcinoma in situ, characterized by filled lumens, are often associated with hypoxic markers. However, the contribution of hypoxia to changes in tissue architecture in early pre-malignant lesions is not well defined. Using three-dimensional basement membrane cultures of mammary epithelial cells, we recently reported that acini-like structures exposed to hypoxia display epithelial disorganization and delayed lumen formation. We found that hypoxia, via HIF-1alpha, targets signaling pathways, specifically the Erk-Bim axis, to suppress anoikis-cell death in a 3D acinar model. Here, we discuss these findings further and present additional data, indicating that hypoxia-mediated alterations in acinar architecture and anoikis-associated Erk-Bim signaling are maintained in mammary epithelial cells after reoxygenation. Taken together, these findings may offer new insight into the contribution of hypoxia-mediated signaling in the progression of early breast cancer lesions and possible treatment of hypoxic cancers.
机译:肿瘤缺氧与化疗耐药,转移发生率增加和临床预后不良有关。早期乳腺癌病变,例如原位癌,其特征是内腔充盈,通常与缺氧标志物有关。但是,低氧对早期恶性前病变组织结构变化的贡献尚不明确。我们最近使用乳腺上皮细胞的三维基底膜培养,我们最近报道,暴露于低氧状态的腺泡状结构表现出上皮组织紊乱和管腔形成延迟。我们发现,通过HIF-1alpha的低氧靶向信号通路,特别是Erk-Bim轴,以抑制3D腺泡模型中的神经细胞死亡。在这里,我们进一步讨论这些发现并提出其他数据,表明在氧合后,在乳腺上皮细胞中保持了缺氧介导的腺泡结构和与神经反应相关的Erk-Bim信号传导的改变。综上所述,这些发现可能为缺氧介导的信号传导在早期乳腺癌病变进展和低氧血症癌症的可能治疗中的作用提供新的见解。

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