{
  "id": 13109748,
  "title": "Tumour-stroma signaling drives a reversible program with neural-like features in cancer-associated fibroblasts",
  "url": "https://urgent.news/2026/10/09/tumour-stroma-signaling-drives-a-reversible-program-with-neural-like",
  "topic": "science",
  "section": "Science",
  "published": "2026-10-09T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.10.07.757165v1?rss=1"
  },
  "original_language": "en",
  "account": "Pancreatic ductal adenocarcinoma (PDAC) is a particularly aggressive cancer, largely due to a dense and adaptable tumor microenvironment primarily composed of cancer-associated fibroblasts (CAFs). Previous research identified a population of CAFs expressing a neural-associated program (NES+SOX4+NOTCH1+) that intensified with disease progression, but the signaling mechanisms behind this state were not well understood. This study aimed to investigate how tumor-derived signals activate this program and determine if it represents a stable fibroblast identity or a reversible one.\n\nBy analyzing spatial transcriptomic data from normal pancreas to invasive carcinoma, researchers identified EGF, FGF2, and BDNF as potential tumor-to-fibroblast signals correlated with disease progression. Functional experiments with patient-derived CAFs and human fibroblast cell lines confirmed that EGF and FGF2 alone are sufficient to induce the NES+SOX4+NOTCH1+ program. Upon withdrawal of these growth factors, the program was reversed at both the protein and transcriptional levels, indicating that this state is dynamic and contingent upon the environment.\n\nFurther single-cell transcriptomic analysis uncovered a multi-phase response, starting with an early loss of fibroblast-associated features, followed by a transient activation of neural-associated genes, and concluding with a later stress-associated state. Regulatory analyses pinpointed ETS-family transcription factors as key regulators of the program, while phosphoproteomic profiling and inhibitor studies revealed that MAPK/ERK signaling plays a central role in its transcriptional activation.\n\nMost intriguingly, pan-cancer single-cell analysis demonstrated that this reversible program is enriched in CAFs and becomes more prevalent from normal to tumor tissue across various cancer types. This study not only defines a dynamic, growth factor-driven fibroblast program but also identifies signaling mechanisms that could potentially allow for the selective modulation of fibroblast states that support tumor growth.",
  "summary": "Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers, in part due to a dense and highly plastic tumor microenvironment dominated by cancer-associated fibroblasts (CAFs). In previous work, we identified a CAF population expressing a neural-associated NES+SOX4+NOTCH1+ program that increased with disease progression. The signals driving this state and the mechanisms…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}