Scholarlink

<p>Squamous cell carcinomas (SCCs) originate in epithelial tissues of older individuals who have been exposed to environmental carcinogens. Despite overlapping clinical hallmarks, SCCs from different anatomic sites have different prognoses. Here we show that fibroblasts confer site-specific cues that determine SCC proliferation and invasion. Oral and lung fibroblasts have distinct lipid metabolism, transferring unique lipids to SCC cells that promote epithelial-to-mesenchymal transition, and oral and lung SCC invasion. Whereas oral fibroblasts transfer sphingomyelins, which activate the ceramide–sphingosine-1-phosphate–STAT3 pathway and promote oral SCC invasion, lung fibroblasts transfer triglycerides to lung SCCs, thereby triggering cholesterol synthesis and invasion, which is associated with poor survival. By contrast, dermal fibroblasts are lipid poor, and cutaneous SCC is less invasive. Our data indicate that targeting fibroblast lipid synthesis and SCC lipid uptake or breakdown inhibits oral and lung epithelial cancer invasion.</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

Tissue-specific fibroblast lipid cues impose the rate of epithelial cancer invasion

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月27日

查看全文
  • Timothy Budden,
  • Noah Palombo,
  • Shilpa Gurung,
  • Martha Gutteridge,
  • Charlotte Russell,
  • Jair Marques,
  • Alex von Kriegsheim,
  • Lyutong An,
  • Catherine Harwood,
  • Luisa Motta,
  • Claus Jorgensen,
  • Carlos López-Garcîa,
  • Caroline Gaudy-Marqueste,
  • Kevin Harrington,
  • Malin Pedersen,
  • Ben O’Leary,
  • Antonio Rullan,
  • Amaya Virós

摘要

Squamous cell carcinomas (SCCs) originate in epithelial tissues of older individuals who have been exposed to environmental carcinogens. Despite overlapping clinical hallmarks, SCCs from different anatomic sites have different prognoses. Here we show that fibroblasts confer site-specific cues that determine SCC proliferation and invasion. Oral and lung fibroblasts have distinct lipid metabolism, transferring unique lipids to SCC cells that promote epithelial-to-mesenchymal transition, and oral and lung SCC invasion. Whereas oral fibroblasts transfer sphingomyelins, which activate the ceramide–sphingosine-1-phosphate–STAT3 pathway and promote oral SCC invasion, lung fibroblasts transfer triglycerides to lung SCCs, thereby triggering cholesterol synthesis and invasion, which is associated with poor survival. By contrast, dermal fibroblasts are lipid poor, and cutaneous SCC is less invasive. Our data indicate that targeting fibroblast lipid synthesis and SCC lipid uptake or breakdown inhibits oral and lung epithelial cancer invasion.