Stromal cells in normal colon and colon cancers: importance of thyroid hormone signaling.

IF 9.6 1区 生物学 Q1 CELL BIOLOGY
Mathieu Reslinger, Michelina Plateroti
{"title":"Stromal cells in normal colon and colon cancers: importance of thyroid hormone signaling.","authors":"Mathieu Reslinger, Michelina Plateroti","doi":"10.1038/s41419-025-08005-0","DOIUrl":null,"url":null,"abstract":"<p><p>Thyroid hormones (THs, namely T3 and T4) regulate intestinal development and homeostasis via thyroid hormone nuclear receptors (TRs), which are T3-modulated transcription factors. Previous work has highlighted the importance of THs and the TRα1 receptor in intestinal stem cell biology and tumor formation, through actions on WNT, NOTCH, and BMP signaling pathways, which mediate epithelial-stromal cell interactions. Recent findings underscore the critical role of stromal cells in maintaining homeostasis and interacting with colonic stem cells. Stromal cells, especially cancer-associated fibroblasts (CAFs), are also essential in colorectal cancer (CRC). While the TH/TR signaling on gut epithelia-stromal interactions is well characterized in amphibians during the TH-dependent metamorphosis process, its function in the normal mammalian colon is still poorly defined, and in CRCs, it remains underexplored. In addition, it is worth underlining that TRα1 mutations in patients are responsible for Resistance to Thyroid Hormone-α (RTH-α) syndrome. This syndrome is a complex pathology that recapitulates typical traits of hypothyroidism, including gut malfunction. Up to now, very little is known about the cellular alterations in the gut of RTH-α patients. This review summarizes recent studies on the roles of T3 and TRα1 in colon physiopathology, with an emphasis on epithelial/stromal or tumor/stromal interactions via cell-cell signaling.</p>","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":"16 1","pages":"699"},"PeriodicalIF":9.6000,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501227/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Death & Disease","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1038/s41419-025-08005-0","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Thyroid hormones (THs, namely T3 and T4) regulate intestinal development and homeostasis via thyroid hormone nuclear receptors (TRs), which are T3-modulated transcription factors. Previous work has highlighted the importance of THs and the TRα1 receptor in intestinal stem cell biology and tumor formation, through actions on WNT, NOTCH, and BMP signaling pathways, which mediate epithelial-stromal cell interactions. Recent findings underscore the critical role of stromal cells in maintaining homeostasis and interacting with colonic stem cells. Stromal cells, especially cancer-associated fibroblasts (CAFs), are also essential in colorectal cancer (CRC). While the TH/TR signaling on gut epithelia-stromal interactions is well characterized in amphibians during the TH-dependent metamorphosis process, its function in the normal mammalian colon is still poorly defined, and in CRCs, it remains underexplored. In addition, it is worth underlining that TRα1 mutations in patients are responsible for Resistance to Thyroid Hormone-α (RTH-α) syndrome. This syndrome is a complex pathology that recapitulates typical traits of hypothyroidism, including gut malfunction. Up to now, very little is known about the cellular alterations in the gut of RTH-α patients. This review summarizes recent studies on the roles of T3 and TRα1 in colon physiopathology, with an emphasis on epithelial/stromal or tumor/stromal interactions via cell-cell signaling.

Abstract Image

Abstract Image

Abstract Image

正常结肠癌和结肠癌的基质细胞:甲状腺激素信号的重要性。
甲状腺激素(THs,即T3和T4)通过甲状腺激素核受体(TRs)调节肠道发育和体内平衡,TRs是T3调节的转录因子。先前的研究强调了THs和TRα1受体在肠道干细胞生物学和肿瘤形成中的重要性,它们通过作用于介导上皮-间质细胞相互作用的WNT、NOTCH和BMP信号通路。最近的研究结果强调了基质细胞在维持体内平衡和与结肠干细胞相互作用中的关键作用。基质细胞,尤其是与癌症相关的成纤维细胞(CAFs),在结直肠癌(CRC)中也是必不可少的。虽然在两栖动物的TH依赖性变态过程中,肠道上皮-间质相互作用的TH/TR信号被很好地表征,但其在正常哺乳动物结肠中的功能仍然不明确,在crc中,它仍未被充分探索。此外,值得强调的是,患者的TRα1突变与甲状腺激素-α抵抗综合征(RTH-α)有关。该综合征是一种复杂的病理,概括了甲状腺功能减退的典型特征,包括肠道功能障碍。到目前为止,对RTH-α患者肠道细胞的改变知之甚少。本文综述了近年来关于T3和TRα1在结肠生理病理中的作用的研究,重点介绍了细胞-细胞信号传导中上皮/基质或肿瘤/基质的相互作用。
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
Cell Death & Disease
Cell Death & Disease CELL BIOLOGY-
CiteScore
15.10
自引率
2.20%
发文量
935
审稿时长
2 months
期刊介绍: Brought to readers by the editorial team of Cell Death & Differentiation, Cell Death & Disease is an online peer-reviewed journal specializing in translational cell death research. It covers a wide range of topics in experimental and internal medicine, including cancer, immunity, neuroscience, and now cancer metabolism. Cell Death & Disease seeks to encompass the breadth of translational implications of cell death, and topics of particular concentration will include, but are not limited to, the following: Experimental medicine Cancer Immunity Internal medicine Neuroscience Cancer metabolism
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信