A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Jagged1 regulates extracellular matrix deposition and remodeling in triple-negative breast cancer
Tekijät: Parikainen, Marjaana; Suwal, Ujjwal; Rappu, Pekka; Heino, Jyrki; Sahlgren, Cecilia M.
Julkaisuvuosi: 2026
Lehti: Science Advances
Artikkelin numero: eaea9562
Vuosikerta: 12
Numero: 12
eISSN: 2375-2548
DOI: https://doi.org/10.1126/sciadv.aea9562
Julkaisun avoimuus kirjaamishetkellä: Avoimesti saatavilla
Julkaisukanavan avoimuus : Kokonaan avoin julkaisukanava
Verkko-osoite: https://doi.org/10.1126/sciadv.aea9562
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/516319618
Rinnakkaistallenteen lisenssi: CC BY
Rinnakkaistallennetun julkaisun versio: Kustantajan versio
The extracellular matrix (ECM) and tumor microenvironment heterogeneity drive cancer progression and treatment resistance. High Jagged1 expression correlates with poor patient survival and promotes tumor growth and invasion in triple-negative breast cancer (TNBC). Using transcriptomics, proteomics, and imaging of cancer cell/fibroblast cocultures in vitro and in vivo, we demonstrate that Jagged1-mediated cross-talk between TNBC cells and fibroblasts enhances myofibroblast activation, collagen accumulation, and alignment of ECM fibers. In single-cell RNA sequencing data of TNBC tumors, high Jagged1 expression gives rise to a myofibroblast subpopulation previously associated with enhanced invasion. Jagged1 increases transforming growth factor–β (TGFβ) activity in fibroblast cocultures, and TGFβ inhibition prevents the Jagged1-induced ECM alignment. Thus, Jagged1 regulates ECM remodeling upstream of TGFβ. Furthermore, higher substrate stiffness up-regulates Jagged1, suggesting a feed-forward loop between Jagged1, ECM stiffness, and TGFβ. With the emergence of safe therapeutics targeting specific Notch components, Jagged1 modulation may offer an approach for treating invasive breast cancer.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
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This work was supported by the following: European Union’s Horizon 2020 research and innovation program grant 953234 (to C.M.S.), Research Council of Finland grant 307133 (to C.M.S. and M.P.), Research Council of Finland grant 309373 (to C.M.S.), Research Council of Finland grant 329743 (to P.R., U.S., and J.H.), Research Council of Finland’s Flagship InFLAMES grants 337531 and 357911, Åbo Akademi University Foundation’s Center of Excellence in Cellular Mechanostasis (to C.M.S.), Cancer Foundation Finland sr (to C.M.S. and M.P.), Jane and Aatos Erkko Foundation (to C.M.S. and M.P.), Sigrid Jusélius Foundation (to C.M.S., J.H., P.R., U.S., and M.P.), Varsinais-Suomi Regional Fund of the Finnish Cultural Foundation (to M.P.), Swedish Cultural Foundation in Finland (to M.P.), K. Albin Johansson Foundation (to M.P.), and Ida Montin Foundation (to M.P.).
