Lung squamous cell carcinoma (LUSC) accounts for approximately 25% to 30% of lung cancers, but largely no targeted therapy is available against it, calling for identification of new oncogenes in LUSC growth for new therapeutic targets. In this study, REL was identified through a screening for oncogenes that are highly amplified in human LUSC. Its expression was associated with poor prognosis in LUSC patients. Furthermore, knockdown of c-Rel in LUSC cell lines lead to significant decrease in cell proliferation and migration. Mechanistically, c-Rel knockdown suppressed NFκB pathway by blocking phosphorylation of IκB. Consistently, pharmaceutic inhibition of c-Rel also. In orthotopic xenograft lung cancer mouse model, c-Rel knockdown inhibited the tumor growth. Cancer cell proliferation and epithelial-mesenchymal-transition (EMT) of the tumors were impaired by c-Rel knockdown. Finally, it's confirmed in precision-cut tumor slices of LUSC that deletion of c-Rel inhibits the NFκB pathway and cancer cell growth. Accordingly, we hypothesize that c-Rel promotes the activation of the NFκB pathway by promoting the phosphorylation of IκB in LUSC. Our study reveals REL as a novel LUSC oncogene and provides new insights into the molecular regulation of LUSC, which will provide new therapeutic targets for the treatment of squamous lung cancer.

中文翻译：

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c-Rel 是肺鳞状细胞癌中调节细胞增殖和迁移的新型癌基因

肺鳞状细胞癌 (LUSC) 约占肺癌的 25% 至 30%，但基本上没有针对它的靶向治疗，需要鉴定 LUSC 生长中的新癌基因以找到新的治疗靶点。在这项研究中，REL 是通过筛选在人类 LUSC 中高度扩增的癌基因而确定的。它的表达与 LUSC 患者的不良预后相关。此外，LUSC细胞系中c-Rel的敲低导致细胞增殖和迁移显着下降。从机制上讲，c-Rel 敲低通过阻断 IκB 磷酸化来抑制 NFκB 通路。一致地，c-Rel 的药物抑制也如此。在原位异种移植肺癌小鼠模型中，c-Rel 敲低抑制了肿瘤生长。c-Rel 敲低会损害癌细胞增殖和肿瘤上皮间质转化 (EMT)。最后，在 LUSC 的精确切割肿瘤切片中证实，c-Rel 的缺失会抑制 NFκB 通路和癌细胞生长。因此，我们假设 c-Rel 通过促进 LUSC 中 IκB 的磷酸化来促进 NFκB 通路的激活。我们的研究揭示了REL作为一种新型LUSC癌基因，为LUSC的分子调控提供了新的见解，这将为鳞状肺癌的治疗提供新的治疗靶点。