Nicotine enhances the stemness and tumorigenicity in intestinal stem cells via Hippo-YAP/TAZ and Notch signal pathway.

IF 6.4 1区生物学 Q1 BIOLOGY

eLife Pub Date : 2025-01-03 DOI:10.7554/eLife.95267

Ryosuke Isotani, Masaki Igarashi, Masaomi Miura, Kyoko Naruse, Satoshi Kuranami, Manami Katoh, Seitaro Nomura, Toshimasa Yamauchi

{"title":"Nicotine enhances the stemness and tumorigenicity in intestinal stem cells via Hippo-YAP/TAZ and Notch signal pathway.","authors":"Ryosuke Isotani, Masaki Igarashi, Masaomi Miura, Kyoko Naruse, Satoshi Kuranami, Manami Katoh, Seitaro Nomura, Toshimasa Yamauchi","doi":"10.7554/eLife.95267","DOIUrl":null,"url":null,"abstract":"<p><p>Cigarette smoking is a well-known risk factor inducing the development and progression of various diseases. Nicotine (NIC) is the major constituent of cigarette smoke. However, knowledge of the mechanism underlying the NIC-regulated stem cell functions is limited. In this study, we demonstrate that NIC increases the abundance and proliferative activity of murine intestinal stem cells (ISCs) in vivo and ex vivo. Moreover, NIC induces Yes-associated protein (YAP) /Transcriptional coactivator with PDZ-binding motif (TAZ) and Notch signaling in ISCs via α7-nicotinic acetylcholine receptor (nAchR) and protein kinase C (PKC) activation; this effect was not detected in Paneth cells. The inhibition of Notch signaling by dibenzazepine (DBZ) nullified the effects of NIC on ISCs. NIC enhances in vivo tumor formation from ISCs after loss of the tumor suppressor gene Apc, DBZ inhibited NIC-induced tumor growth. Hence, this study identifies a NIC-triggered pathway regulating the stemness and tumorigenicity of ISCs and suggests the use of DBZ as a potential therapeutic strategy for treating intestinal tumors.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4000,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11698494/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"eLife","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.7554/eLife.95267","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Cigarette smoking is a well-known risk factor inducing the development and progression of various diseases. Nicotine (NIC) is the major constituent of cigarette smoke. However, knowledge of the mechanism underlying the NIC-regulated stem cell functions is limited. In this study, we demonstrate that NIC increases the abundance and proliferative activity of murine intestinal stem cells (ISCs) in vivo and ex vivo. Moreover, NIC induces Yes-associated protein (YAP) /Transcriptional coactivator with PDZ-binding motif (TAZ) and Notch signaling in ISCs via α7-nicotinic acetylcholine receptor (nAchR) and protein kinase C (PKC) activation; this effect was not detected in Paneth cells. The inhibition of Notch signaling by dibenzazepine (DBZ) nullified the effects of NIC on ISCs. NIC enhances in vivo tumor formation from ISCs after loss of the tumor suppressor gene Apc, DBZ inhibited NIC-induced tumor growth. Hence, this study identifies a NIC-triggered pathway regulating the stemness and tumorigenicity of ISCs and suggests the use of DBZ as a potential therapeutic strategy for treating intestinal tumors.

查看原文本刊更多论文

尼古丁通过Hippo-YAP/TAZ和Notch信号通路增强肠干细胞的干性和致瘤性。

吸烟是一个众所周知的危险因素，可诱发各种疾病的发生和发展。尼古丁（NIC）是香烟烟雾的主要成分。然而，对nic调节的干细胞功能的机制的了解是有限的。在这项研究中，我们证明了NIC在体内和离体中增加了小鼠肠道干细胞（ISCs）的丰度和增殖活性。此外，NIC通过α7-烟碱乙酰胆碱受体（nAchR）和蛋白激酶C （PKC）激活，诱导ISCs中含有pdz结合基序的yes相关蛋白(YAP) /转录共激活因子（TAZ）和Notch信号通路；在Paneth细胞中没有检测到这种效应。二苯二氮平（DBZ）对Notch信号的抑制作用抵消了NIC对ISCs的影响。在失去肿瘤抑制基因Apc后，NIC促进体内ISCs肿瘤的形成，DBZ抑制NIC诱导的肿瘤生长。因此，本研究确定了nic触发的调节ISCs干性和致瘤性的途径，并建议使用DBZ作为治疗肠道肿瘤的潜在治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

eLife BIOLOGY-

CiteScore

12.90

自引率

3.90%

发文量

3122

审稿时长

17 weeks

期刊介绍： eLife is a distinguished, not-for-profit, peer-reviewed open access scientific journal that specializes in the fields of biomedical and life sciences. eLife is known for its selective publication process, which includes a variety of article types such as: Research Articles: Detailed reports of original research findings. Short Reports: Concise presentations of significant findings that do not warrant a full-length research article. Tools and Resources: Descriptions of new tools, technologies, or resources that facilitate scientific research. Research Advances: Brief reports on significant scientific advancements that have immediate implications for the field. Scientific Correspondence: Short communications that comment on or provide additional information related to published articles. Review Articles: Comprehensive overviews of a specific topic or field within the life sciences.