A groundbreaking study led by Professor Cecilia Sahlgren and her team at Åbo Akademi University in Finland, alongside the InFLAMES Research Flagship, has unveiled a novel mechanism that orchestrates detrimental remodeling of tumor tissue during the progression of breast cancer. This pivotal discovery paves the way for innovative therapeutic avenues targeting aggressive breast cancer variants, particularly those that are notoriously resistant due to a lack of targeted treatment options.
Breast cancer remains the most prevalent malignancy among women globally, manifesting a wide spectrum of clinical outcomes. Early-stage, localized breast cancer typically boasts favorable prognoses, yet the advent of metastatic dissemination drastically diminishes survival prospects. While factors such as cancer subtype and hormone receptor status have long been recognized for their prognostic value, emerging evidence emphasizes the critical role of intercellular communication within the tumor microenvironment. This complex cellular crosstalk enables cancer cells to manipulate their surroundings, facilitating metastatic spread and resistance to conventional therapies.
Central to this communication network is the protein Jagged1, previously identified as highly expressed in aggressive, hormone receptor-negative breast cancers. However, the specific functional contributions of Jagged1 in breast cancer progression had remained elusive until now. In their novel investigation, doctoral researcher Marjaana Parikainen and colleagues demonstrate that Jagged1 not only exacerbates tumor growth but also accelerates metastasis, correlating with poorer survival in patients afflicted with aggressive breast cancer phenotypes.
Employing a comprehensive array of cancer models enriched by clinical breast cancer patient data, the research team uncovered an uncharted mode of cellular dialogue between malignant breast cells and fibroblasts mediated by Jagged1. Fibroblasts, the architects of the extracellular matrix (ECM), play a fundamental role in maintaining tissue architecture and regulating cellular behavior through the ECM’s structural components and signaling molecules. The study reveals that the presence of Jagged1 on breast cancer cells spurs adjacent fibroblasts into an activated state that elevates the production of collagen and remodels the ECM to favor tumor progression.
This Jagged1-induced fibroblast activation leads to pronounced structural alterations in the ECM, notably the alignment of collagen fibers into linear tracks. These aligned fibers act as conduits, facilitating directional migration of cancer cells and thereby enhancing their metastatic potential. Such matrix remodeling significantly influences tissue stiffness — a biomechanical property long recognized to impact cancer cell behavior and therapy response.
Delving deeper into the molecular cascade, the researchers illuminated a critical link between Jagged1 expression and the activation of the transforming growth factor beta (TGFβ) signaling pathway. TGFβ is an established master regulator implicated in late-stage breast cancer progression, known for promoting fibrosis, elevating matrix stiffness, and fostering metastatic dissemination. Their findings reveal that Jagged1 amplifies TGFβ activity, leading to intensified collagen deposition and ECM linearization, thereby creating a microenvironment conducive to cancer cell invasion.
Remarkably, the study also uncovers a self-perpetuating feedback loop where increased matrix stiffness further upregulates Jagged1 expression on cancer cells. This mechanosensitive response, coupled with TGFβ’s known role in inducing Jagged1, establishes a vicious cycle that continuously drives tumor aggression and remodeling. Consequently, the tumor microenvironment evolves dynamically, reinforcing malignant phenotypes and fostering therapeutic resistance.
The implications of these insights are profound, not only deepening our understanding of the tumor-stroma interplay but also highlighting Jagged1 as a promising therapeutic target. Interrupting this feedback mechanism could disrupt the pro-tumorigenic remodeling of the ECM, impeding metastasis and potentially enhancing the efficacy of existing treatments for triple-negative and hormone receptor-negative breast cancers, which currently pose significant clinical challenges.
Collaboration with Professor Jyrki Heino’s research group at the University of Turku fortified the multidisciplinary approach of this investigation, combining expertise in cell biology, extracellular matrix biochemistry, and oncology. Funding support from prominent Finnish foundations and the Research Council of Finland underscores the national commitment to combating breast cancer through innovative research.
Published in the high-impact journal Science Advances on March 18, 2026, this study marks a significant advance in cancer biology. It underscores the necessity of targeting not only cancer cells but also their microenvironmental communication networks and biomechanical context to achieve comprehensive cancer control.
Looking forward, the elucidation of Jagged1’s role invites further exploration into the development of inhibitors or modulators that can selectively target this molecular interaction axis. Such targeted therapies could revolutionize management strategies for aggressive breast cancer forms, aligning with the broader aims of personalized medicine.
The InFLAMES Research Flagship’s integrative approach exemplifies the power of combining immunological and molecular research to unlock novel diagnostic and therapeutic pathways. As more is uncovered about tumor microenvironment dynamics, it becomes increasingly evident that multi-faceted intervention strategies will be key to overcoming cancer metastasis and resistance.
For further information, inquiries can be directed to doctoral researcher Marjaana Parikainen or Professor Cecilia Sahlgren at Åbo Akademi University, whose contact details are available to facilitate academic collaborations and media engagement.
Subject of Research: Cells
Article Title: Jagged1 regulates extracellular matrix deposition and remodeling in triple-negative breast cancer
News Publication Date: 18-Mar-2026
Web References: 10.1126/sciadv.aea9562
Keywords: Breast Cancer, Jagged1, Tumor Microenvironment, Extracellular Matrix, Fibroblasts, TGFβ Pathway, Metastasis, Matrix Remodeling, Cancer Progression, Triple-Negative Breast Cancer, Tumor Stiffness, Cell–Cell Communication
