Apr 02, 2026
Researchers from Cambridge and Dresden uncover a new molecular mechanism driving early tumor growth
Early tumor cells reshape the surrounding support tissue to create a microenvironment that helps them survive and grow, involving connective tissue, fibroblasts and immune cells in this transformation.
As we age, mutations that can trigger cancer accumulate in otherwise healthy tissues. Yet only a small fraction of these altered cells actually develop into tumors. Recent studies suggest that tumor formation depends on complex interactions between mutated cells and their surrounding environment, but the underlying processes and contributing factors have remained poorly understood. An international research team led by the University of Cambridge, with contributions from the Faculty of Medicine at TUD Dresden University of Technology and the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) has now described a previously unknown mechanism that promotes the survival of tumor cells at a very early stage.
The study, recently published in Nature, investigates why some microscopic tumors disappear shortly after they emerge, while others persist and later progress to cancer. To address this question, the team led by Dr. Maria P. Alcolea (Cambridge Stem Cell Institute), modeled the earliest stages of tumor development in the mouse esophagus. The researchers identified the rare tumors that escape the tissue’s natural protective barriers and analyzed what distinguishes them from the many others that are eliminated early on. Their focus was on the epithelial tissue, which covers and protects both external and internal body surfaces.
Most new tumors in the esophagus are quickly outcompeted and displaced by surrounding healthy cells. However, the new study shows that early epithelial tumor cells send stress signals to the underlying tissue as they emerge. These signals activate fibroblasts in the lamina propria – a thin layer of connective tissue – in a manner similar to wound‑healing responses. The activated fibroblasts assemble a protective scaffold around the initially intraepithelial lesion, which is still confined to the uppermost cell layer. This process creates a specialized microenvironment known as a “precancerous niche,” which supports the survival and growth of the nascent tumor.
At the molecular level, this mechanism is driven by an EGF–SOX9–FN1 signaling axis that regulates cell behavior and growth. When the researchers disrupted the molecular communication between the two tissue compartments, the precancerous niche failed to form, and significantly fewer early tumors survived.
Analyses of human tissue confirmed these findings: early tumor cells in the human esophagus also displayed characteristic stress signals and were surrounded by the same fibrotic scaffold. These insights may improve early detection of esophageal cancer, a disease that is often diagnosed only at advanced stages when treatment options are limited.
The study involved Prof. József Jászai and Prof. Mirko HH Schmidt from the Institute of Anatomy at the TUD Faculty of Medicine as well as Prof. Daniela Aust from the Institute of Pathology at the University Hospital Dresden. The Dresden teams provided human tissue samples from patients with esophageal cancer and performed the corresponding pathological analyses. The samples were carefully selected, processed, and examined using histological and immunohistological methods to compare tumor tissue with healthy tissue. Their contributed to validating the mechanisms discovered in the mouse model and demonstrate their relevance in early stages of human esophageal cancer.
The findings show that tumor survival is determined not only by genetic alterations but also by interactions between mutated cells and their immediate environment. These characteristic “precancerous niches” could serve as early biological indicators to detect emerging tumors at an earlier stage.
Prof. Esther Troost, Dean of the Faculty of Medicine, states: “Identifying precancerous niches as a prerequisite for the survival of early tumor cells is an important finding for future cancer therapies. The fact that research teams in Dresden were able to confirm these mechanisms in human tissue strengthens our oncology focus and highlights the exceptional expertise of our site in translational cancer research.”
Original publication:
Skrupskelyte, G. et al. Precancerous niche remodeling dictates nascent tumor persistence. Nature; 4 March 2026; DOI: 10.1038/s41586-026-10157-8.
Background
The Carl Gustav Carus Faculty of Medicine at TUD Dresden University of Technology is one of Germany’s youngest and most dynamic medical faculties. It sets national and international standards in oncology, metabolic diseases, and neurological and psychiatric disorders. Together with the University Hospital Dresden, the faculty forms Dresden University Medicine, a leading center for patient‑oriented research and modern clinical care.
The Institute of Anatomy at the TUD Faculty of Medicine studies molecular signal transduction processes mediated by secreted or membrane-bound proteins. The institute uses a variety of bioscientific methods, including biochemical analyses, advanced imaging, in vivo models, and the study of human samples. The Institute of Pathology at the University Hospital Dresden examines approximately 48,000 tissue samples each year from surgical and nonsurgical procedures. Using histological, immunohistological, and molecular pathological techniques, the institute performs biopsy and autopsy diagnostics, covering the full spectrum, and is a key partner for clinical departments.
Scientific contact:
Prof. József Jászai
Institute of Anatomy of the Carl Gustav Carus Faculty of Medicine
at the TUD Dresden University of Technology
Phone: +49 (0) 351 458 6085
Email:
Contact for the media:
Anne-Stephanie Vetter
Staff Unit Public Relations
Carl Gustav Carus Faculty of Medicine
of the TUD Dresden University of Technology
Phone +49 (0) 351 458 17903
Email: