A Succony, Laura Gómez-López, Sandra penycuick, Adam Alhendi, Ahmed S. N. A Davies, Derek Clarke, Sarah E. A Gowers, Kate H.C. A Wright, Nicholas A Jensen, Kim B. A Janes, Sam M. TLrig1表达识别具有高增殖能力的气道基底细胞并限制肺鳞状细胞癌的生长%D 2021 %R 10.183 /13993003.00816-2020 %J European Respiratory Journal %P 2000816 %X肺鳞状细胞癌(LUSC)占全球癌症死亡的重要比例。在此之前，气道上皮中出现进行性紊乱的侵袭前病变。然而，侵袭前病变进展为侵袭性LUSC的生物学机制尚不完全清楚。LRIG1在侵袭前气道病变和侵袭性LUSC肿瘤中下调，这与肺癌患者生存率降低相关。利用在支气管镜下收集的Lrig1敲入报告细胞小鼠和人气道上皮细胞，我们发现在稳态期间，Lrig1在气道上皮细胞中异质性表达。在被怀疑是LUSC起源的基础气道上皮细胞中，LRIG1在小鼠和人体内鉴定了一个具有更高体外增殖和自我更新潜能的祖细胞亚群。利用n -亚硝基三氯乙基脲(NTCU)诱导的LUSC小鼠模型，我们发现Lrig1功能缺失导致在侵袭前疾病的早期阶段异常高的细胞增殖，并形成明显更大的侵袭性肿瘤，提示疾病加速进展。总之，我们的研究结果确定LRIG1是具有高增殖潜力的基础气道祖细胞的标记物，并作为侵袭前肺癌进展的调节剂。这项工作强调了LRIG1的临床相关性，以及ntcu诱导的LUSC模型在候选肿瘤抑制子和癌基因功能评估中的潜力。脚注本手稿最近已被接受发表在欧洲呼吸杂志。在我们的制作团队进行编辑和排版之前，它以接受的形式在这里发表。在这些生产过程完成后，作者已经批准了结果的证明，文章将移动到最新一期的ERJ在线。 Please open or download the PDF to view this article.Conflict of interest: Dr. Succony reports grants from Wellcome Trust, grants from Cancer Research UK, during the conduct of the study.Conflict of interest: Dr. Gómez López reports grants from The Royal Society, during the conduct of the study.Conflict of interest: Dr. Pennycuick reports grants from Wellcome Trust, during the conduct of the study; In addition, Dr. Pennycuick has a patent United Kingdom Patent Application No. 1819452.2 pending.Conflict of interest: Dr. Alhendi has nothing to disclose.Conflict of interest: Dr. Davies has nothing to disclose.Conflict of interest: Dr. Clarke reports grants from NIHR UCLH BRC, during the conduct of the study.Conflict of interest: Dr. Gowers has nothing to disclose.Conflict of interest: Dr. Wright reports grants from Cancer Research UK, outside the submitted work.Conflict of interest: Dr. Jensen has nothing to disclose.Conflict of interest: Dr. Janes reports grants from Wellcome, during the conduct of the study; personal fees from Jansen, grants from GRAIL Inc, personal fees from Astra Zeneca, outside the submitted work. %U //www.qdcxjkg.com/content/erj/early/2021/07/29/13993003.00816-2020.full.pdf