Scholarlink

<p>The <i>Drosophila</i> 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 <i>Toll</i> in regulating intestinal stem cell activity through direct transcriptional control of <i>PI3K</i> and <i>Akt</i> in an insulin-independent manner. Time-series transcriptomic analysis of intestinal damage and repair responses reveals that the stress-responsive factor <i>Jumu</i> regulates <i>Spz</i> 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 <i>Toll</i>. 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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Toll signaling controls stem cell proliferation in intestinal regeneration and tumorigenesis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月3日

查看全文
  • Guofan Peng,
  • Shichao Yang,
  • Yuexia Zhang,
  • Yu Zhao,
  • Xiaoyun Huang,
  • Shengen Yi,
  • Lei Gu,
  • Ganqian Zhu,
  • Kewei Zheng,
  • Huijun Zhou,
  • Kang Han,
  • Jun Zhou

摘要

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.