Myeloid cell RelA/p65 promotes lung cancer proliferation through Wnt/β-catenin signaling in murine and human tumor cells
Myeloid cell RelA/p65 promotes lung cancer proliferation through Wnt/β-catenin signaling in murine and human tumor cells
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DOI：
10.1038/onc.2013.75
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发表时间：
2014-03-06
期刊：
影响因子：
8
通讯作者：
Bals, R.
中科院分区：
文献类型：
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作者：
Li, D.;Beisswenger, C.;Bals, R.
吸烟是肺癌（LC）和慢性阻塞性肺疾病最重要的危险因素。本研究旨在探讨髓细胞核因子κ B在肿瘤细胞生长信号调控中的作用。我们将缺乏髓系RelA/p65 （RelA (δ -/-)）的小鼠置于转移性LC模型中。香烟烟雾（CS）暴露显著增加野生型小鼠Lewis肺癌细胞肿瘤的增殖。在cs暴露的rela（Delta-/-）小鼠中，肿瘤生长受到很大程度的抑制。肿瘤组织的转录组和通路分析揭示了骨髓细胞对多种生长信号通路的基本影响，包括Wnt/ β -catenin通路。综上所述，髓系RelA/p65是将烟雾诱导的炎症与LC生长联系起来所必需的，并在肿瘤细胞中激活Wnt/ β -catenin信号通路中发挥作用。
Smoking is the most important risk factor for both lung cancer (LC) and chronic obstructive pulmonary disease. The aim of this study was to investigate the role of myeloid cell nuclear factor-kappa B in the regulation of tumor cell growth signaling. We subjected mice lacking myeloid RelA/p65 (rela(Delta-/-)) to a metastatic LC model. Cigarette smoke (CS) exposure significantly increased the proliferation of Lewis lung carcinoma cell tumors in wild-type mice. In CS-exposed rela(Delta-/-) mice, the tumor growth was largely inhibited. Transcriptome and pathway analysis of cancer tissue revealed a fundamental impact of myeloid cells on various growth signaling pathways, including the Wnt/beta-catenin pathway. In conclusion, myeloid RelA/p65 is necessary to link smoke-induced inflammation with LC growth and has a role in the activation of Wnt/beta-catenin signaling in tumor cells.