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Wnt/beta-catenin signaling inhibits death receptor-mediated apoptosis and promotes invasive growth of HNSCC

机译:Wnt /β-catenin信号传导抑制死亡受体介导的凋亡并促进HNSCC的侵袭性生长

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The Wnt/beta-catenin signaling pathway plays a critical role in cell proliferation and oncogenesis. It has been found to be chronically activated in a variety of human cancers, including head and neck squamous cell carcinoma (HNSCC). Previously, we have found that the activation of the Wnt/beta-catenin signaling pathway inhibits mitochondria-mediated apoptosis. In this study, we extended our studies to determine whether the Wnt/beta-catenin signaling pathway inhibited death receptor-mediated apoptosis in HNSCC cells. We found that Wnt/pcatenin inhibited not only tumor necrosis factor (TNF)/c-Myc-mediated apoptosis, but also cell detachment-mediated apoptosis (anoikis) which is dependent on the death receptor signaling pathway. Interestingly, we also observed that the Wnt/beta-catenin signaling pathway induced HNSCC cell scattering and promoted cell invasion in the Matrigel, both of which are hallmarks for the invasive growth of HNSCC. Consistently, the over-expression of beta-catenin promoted HNSCC tumor growth in nude inice. Taken together, our results suggest that the Wnt/ beta-catenin signaling pathway plays dual functions in HNSCC development: promoting both cell survival and invasive growth of HNSCC cells. (c) 2005 Published by Elsevier Inc.
机译:Wnt /β-catenin信号通路在细胞增殖和肿瘤发生中起关键作用。已经发现它在包括头颈部鳞状细胞癌(HNSCC)在内的多种人类癌症中被慢性激活。以前,我们已经发现Wnt /β-catenin信号通路的激活抑制了线粒体介导的细胞凋亡。在这项研究中,我们扩展了研究范围,以确定Wnt /β-catenin信号通路是否抑制HNSCC细胞中死亡受体介导的凋亡。我们发现Wnt / pcatenin不仅抑制肿瘤坏死因子(TNF)/ c-Myc介导的细胞凋亡,而且抑制依赖于死亡受体信号通路的细胞脱离介导的细胞凋亡(anoikis)。有趣的是,我们还观察到Wnt /β-catenin信号通路在基质胶中诱导HNSCC细胞散射并促进细胞侵袭,这两者都是HNSCC侵袭性生长的标志。一致地,β-catenin的过表达促进了裸鼠体内HNSCC肿瘤的生长。两者合计,我们的结果表明Wnt /β-catenin信号通路在HNSCC的发展中起着双重作用:既促进细胞存活又促进HNSCC细胞的侵袭性生长。 (c)2005年由Elsevier Inc.发布。

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