Liang Xiong, Ying Xu, Zhaoya Gao, Jingyi Shi, Yunfan Wang, Xiaodong Wang, Wensheng Huang, Ming Li, Longteng Wang, Jun Xu, Cheng Li, Jin Gu, Hongkui Deng, Molong Qu
{"title":"A patient-derived organoid model captures fetal-like plasticity in colorectal cancer.","authors":"Liang Xiong, Ying Xu, Zhaoya Gao, Jingyi Shi, Yunfan Wang, Xiaodong Wang, Wensheng Huang, Ming Li, Longteng Wang, Jun Xu, Cheng Li, Jin Gu, Hongkui Deng, Molong Qu","doi":"10.1038/s41422-025-01139-y","DOIUrl":null,"url":null,"abstract":"<p><p>Phenotypic plasticity is a hallmark feature driving cancer progression, metastasis, and therapy resistance. Fetal-like transcriptional programs have been increasingly implicated in promoting plastic cell states, yet their roles remain difficult to study due to limitations of existing culture models. Here, we establish a chemically defined patient-derived organoid system that enables long-term expansion of colorectal cancer (CRC) cells while preserving fetal-like features associated with phenotypic plasticity. Using this model, we identify an oncofetal state (OnFS) that is enriched in advanced tumors and linked to key features of plasticity, including epithelial-mesenchymal plasticity, as well as increased metastasis and treatment resistance. Mechanistically, we show that FGF2-AP-1 signaling maintains the OnFS program and associated phenotypic plasticity in CRC. This model offers a powerful platform for studying the fetal-like features underlying cancer cell plasticity and their role in tumor progression and treatment resistance in CRC.</p>","PeriodicalId":9926,"journal":{"name":"Cell Research","volume":" ","pages":""},"PeriodicalIF":28.1000,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Research","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1038/s41422-025-01139-y","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
Phenotypic plasticity is a hallmark feature driving cancer progression, metastasis, and therapy resistance. Fetal-like transcriptional programs have been increasingly implicated in promoting plastic cell states, yet their roles remain difficult to study due to limitations of existing culture models. Here, we establish a chemically defined patient-derived organoid system that enables long-term expansion of colorectal cancer (CRC) cells while preserving fetal-like features associated with phenotypic plasticity. Using this model, we identify an oncofetal state (OnFS) that is enriched in advanced tumors and linked to key features of plasticity, including epithelial-mesenchymal plasticity, as well as increased metastasis and treatment resistance. Mechanistically, we show that FGF2-AP-1 signaling maintains the OnFS program and associated phenotypic plasticity in CRC. This model offers a powerful platform for studying the fetal-like features underlying cancer cell plasticity and their role in tumor progression and treatment resistance in CRC.
期刊介绍:
Cell Research (CR) is an international journal published by Springer Nature in partnership with the Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences (CAS). It focuses on publishing original research articles and reviews in various areas of life sciences, particularly those related to molecular and cell biology. The journal covers a broad range of topics including cell growth, differentiation, and apoptosis; signal transduction; stem cell biology and development; chromatin, epigenetics, and transcription; RNA biology; structural and molecular biology; cancer biology and metabolism; immunity and molecular pathogenesis; molecular and cellular neuroscience; plant molecular and cell biology; and omics, system biology, and synthetic biology. CR is recognized as China's best international journal in life sciences and is part of Springer Nature's prestigious family of Molecular Cell Biology journals.