ArticleEMBO reports2026
Toll signaling controls stem cell proliferation in intestinal regeneration and tumorigenesis.
Guofan Peng, Shichao Yang, Yuexia Zhang, Yu Zhao, Xiaoyun Huang, Shengen Yi, Lei Gu, Ganqian Zhu, Kewei Zheng, Huijun Zhou and 2 more
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In one paragraphArticle in EMBO reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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12 authors.
Guofan Peng *The Affiliated XiangTan Central Hospital of Hunan University, School of Biomedical Sciences, Hunan University, Changsha, 410082, Hunan Province, China.ORCID 0000-0001-8949-258X Shichao Yang *The Affiliated XiangTan Central Hospital of Hunan University, School of Biomedical Sciences, Hunan University, Changsha, 410082, Hunan Province, China.
Yuexia Zhang *The Affiliated XiangTan Central Hospital of Hunan University, School of Biomedical Sciences, Hunan University, Changsha, 410082, Hunan Province, China.
Yu ZhaoThe Affiliated XiangTan Central Hospital of Hunan University, School of Biomedical Sciences, Hunan University, Changsha, 410082, Hunan Province, China.
Shengen YiDepartment of General Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China.
Lei GuEpigenetics Laboratory, Max Planck Institute for Heart and Lung Research, 61231, Bad Nauheim, Germany.ORCID 0000-0001-6469-9568 Ganqian ZhuThe Affiliated XiangTan Central Hospital of Hunan University, School of Biomedical Sciences, Hunan University, Changsha, 410082, Hunan Province, China.
Kewei ZhengThe Affiliated XiangTan Central Hospital of Hunan University, School of Biomedical Sciences, Hunan University, Changsha, 410082, Hunan Province, China.ORCID 0000-0002-4110-4776 Huijun ZhouGastroenterology Department 1,The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, 410013, Hunan, China. zhouhuijun@hnca.org.cn.ORCID 0009-0008-3534-1469 Kang HanThe Affiliated XiangTan Central Hospital of Hunan University, School of Biomedical Sciences, Hunan University, Changsha, 410082, Hunan Province, China. hankang1988@hnu.edu.cn.ORCID 0009-0005-5613-8329 Jun ZhouThe Affiliated XiangTan Central Hospital of Hunan University, School of Biomedical Sciences, Hunan University, Changsha, 410082, Hunan Province, China. junzhou82@hnu.edu.cn.ORCID 0009-0003-7848-3612 Funding
Department of Science and Technology of Hunan Province (HSTD) 2023JJ0007Department of Science and Technology of Hunan Province (HSTD) 2023JJ20023Department of Science and Technology of Hunan Province (HSTD) 20241226039HSTD | Natural Science Foundation of Hunan Province () 2025JJ30008Key Research and Development Program of Hunan Province of China () 2024JK2108Ministry of Health of China | Wu Jieping Medical Foundation (WJMF) 320.6750.2023-19-30MOST | National Natural Science Foundation of China (NSFC) 32270890MOST | National Natural Science Foundation of China (NSFC) 82200198MOST | National Natural Science Foundation of China (NSFC) 82370177
6 · The paper itselfAbstract
The Drosophila Toll/NF-κB pathway has been extensively studied for its roles in innate immunity and embryonic development. Nevertheless, the regulatory mechanisms underlying Spz/Toll signaling in non-immune contexts remain poorly understood. Here, we demonstrate a critical role for Toll in regulating intestinal stem cell activity through direct transcriptional control of PI3K and Akt in an insulin-independent manner. Time-series transcriptomic analysis of intestinal damage and repair responses reveals that the stress-responsive factor Jumu regulates Spz expression to activate Toll signaling. Disruption of the Jumu/Spz/Toll cascade or PI3K/Akt signaling impairs intestinal regeneration and suppresses tumor growth, and epistasis analysis confirms that PI3K/Akt functions downstream of Toll. Our findings elucidate an autocrine Spz/Toll-mediated mechanism that drives stem cell function via the PI3K/Akt pathway during tissue homeostasis and uncover a critical non-immune role of Toll signaling in both physiological and pathological contexts.
Indexed as
CarcinogenesisDrosophila ProteinsIntestinesRegenerationSignal TransductionStem CellsToll-Like ReceptorsAnimalsCell ProliferationDrosophilaDrosophila melanogasterPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktTranscription FactorsDrosophila ProteinsPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktTl protein, DrosophilaToll-Like ReceptorsTranscription FactorsAkt/PI3K SignalingDrosophilaIntestinal Stem CellToll/TLRs SignalingTumorigenesis
Identifiers
PMID41634381
PMCPMC12979810
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