2026-04-17T11:34:03Zhttps://riubu.ubu.es/oai/request

oai:riubu.ubu.es:10259/106482025-07-03T00:05:33Zcom_10259_6168com_10259_5086com_10259_2604col_10259_6169

Bullock, Esme 2228986e-43b2-481d-a830-ff29b5ad2948 500 Rozyczko, Aleksandra d749e8dd-2d7b-4ac3-92f0-ff7110859617 500 Shabbir, Sana 7e066d51-ebf2-48b0-a88b-598357daf2ca 500 Tsoupi, Ifigenia e5af7464-0c7c-4f8e-a50a-4b54bfeba112 500 Young, Adelaide I.J. bfcaaee1-f896-445e-bc8c-507b293bad67 500 Travnickova, Jana 3b9a1351-0f9a-4468-9780-51b5b1840fc0 500 Gómez Cuadrado, Laura 928 600 0000-0002-4754-2582 Mabruk, Zeanap b2ce4fa6-6c6b-4df9-8ce7-983022a804ea 500 Carrasco, Giovana 158dce06-dda1-4567-84bc-f9e4c4fe2fbe 500 Morrow, Elizabeth 960145dc-8f3d-4500-b9c3-48648463b39a 500 Pennel, Kathryn 1cb9278c-dd55-40db-8cf5-8cf473163f45 500 Kloosterman, Pim ba0f74b3-2da2-406f-bbec-36c936762546 500 Houthuijzen, Julia M 38adfddb-61e7-4517-a7d3-a0c4e710b97b 500 Jonkers, Jos 2fc0b15b-0064-4057-b273-4c6573f64a2f 500 Avalle, Lidia 7d0894de-4700-4ba4-a352-c93cf7de8043 500 Poli, Valeria 94a4c3e9-3aff-4aa4-a792-3cce4898eaef 500 Iggo, Richard 182e0e66-ac89-4aa1-9397-3c977b4747e9 500 Xiao, Xue 73cf1739-b30c-435c-a656-4179086c9816 500 Guo, Jingjing fc86d8aa-f841-45c4-a1c3-563b9f1a1673 500 Zhu, Xuan 69026810-e25f-4a85-ba83-6fa040070c4d 500 Mallon, Elizabeth 615c90eb-6465-4156-a0d7-15be20294e85 500 Edwards, Joanne beee3386-4db9-42a2-9977-88ad9413acbe 500 Patton, E. Elizabeth ed8b0265-e97a-457b-b3d5-abbee8f28fe3 500 Brunton, Valerie G. 647cce9b-b9ca-4776-9053-5bfb5be6858d 500 2025-07-02T10:21:14Z 2025-07-02T10:21:14Z 2025-07 1465-5411 https://hdl.handle.net/10259/10648 10.1186/s13058-025-02074-x 1465-542X Background: Invasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer after invasive ductal carcinoma of no special type (NST), accounting for 10–15% of diagnoses. Despite the myriad molecular, histological and clinical differences between ILC and NST tumors, patients are treated in the same way, and although prognosis initially is good, ILC patients have poorer long-term outcomes. Understanding the differences between these two subtypes and identifying ILC-enriched therapeutic targets is necessary to improve patient care. Methods: Human and mouse cancer-associated fibroblasts (CAFs), ILC cell lines and patient-derived organoids were used for in vitro and in vivo studies, including western blotting, migration, organotypic invasion assays and dissemination in zebrafish embryos. RNASeq was used to identify CAF and interleukin-6 (IL-6)-derived gene signatures. Bioinformatic analysis of public databases and immunohistochemical of human tumor microarrays was carried out. Results: We identified IL-6 as a paracrine CAF-derived factor that activates Signal-Transducer-and-Activator-of-Transcription-3 (STAT3) in human and mouse ILC models. Analysis of human breast tumors showed that the IL-6/JAK/STAT3 pathway is enriched in ER + ILC compared to ER + NST. A 42-gene CAF dependent IL-6 gene signature and 64-gene consensus IL-6 gene signature were generated and were significantly enriched in ER + ILC, with many of the genes overexpressed in ILC tumors. IL-6 treatment suppressed downstream estrogen signaling and also led to the acquisition of a more mesenchymal-like phenotype associated with increased migration and invasion. Finally, IL-6 treatment significantly increased ILC cell dissemination following injection into zebrafish embryos. Conclusions: CAF-derived IL-6 drives paracrine activation of the IL6/JAK/STAT3 signaling pathway which is enriched in ILC. This leads to the acquisition of pro-tumorigenic phenotypes, highlighting the pathway as a potential therapeutic target in ILC. This work was funded by Cancer Research UK (C157/A24837) to V.G.B. and (CANTAC721\100018) to E.B.; an NHS Lothian Charity award (S3181) to V.G.B; an Endeavour Scholarship (734/2018/878) to Z.M.; Punjab Educational Endowment Funds, Pakistan-programme 2020–2024 to S.S.; Medical Research Council (MC_UU_00035/13), Melanoma Research Alliance and Rosetrees Trust (MRA Awards 68730 and 917226) to E.E.P.; Sichuan Science and Technology Program (NO. 2022YFS0601) and Sichuan Provincial People’s Hospital to X.X. This work was supported by the Cancer Research UK Scotland Centre (CTRQQR-2021\100006). application/pdf eng BioMed Central Breast Cancer Research. 2025, V. 27, n. 121 https://doi.org/10.1186/s13058-025-02074-x Atribución 4.0 Internacional http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess Mamas-Cáncer Breast-Cancer Cancer-associated fibroblast driven paracrine IL-6/STAT3 signaling promotes migration and dissemination in invasive lobular carcinoma info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Breast Cancer Research 27 121 THUMBNAIL Bullock-bcr_2025.pdf.jpg Bullock-bcr_2025.pdf.jpg IM Thumbnail image/jpeg 4598 https://riubu.ubu.es/bitstream/10259/10648/4/Bullock-bcr_2025.pdf.jpg 3670c6137c5bdf41c6ff48623f480857 MD5 4 LICENSE license.txt license.txt text/plain; charset=utf-8 1362 https://riubu.ubu.es/bitstream/10259/10648/3/license.txt 5d013bfa6e473ff0db22cd82a4d71a70 MD5 3 CC-LICENSE license_rdf license_rdf application/rdf+xml; charset=utf-8 908 https://riubu.ubu.es/bitstream/10259/10648/2/license_rdf 0175ea4a2d4caec4bbcc37e300941108 MD5 2 ORIGINAL Bullock-bcr_2025.pdf Bullock-bcr_2025.pdf application/pdf 3211356 https://riubu.ubu.es/bitstream/10259/10648/1/Bullock-bcr_2025.pdf 3411d2f64e5c4561abbf7d4931fb8d9e MD5 1 10259/10648 oai:riubu.ubu.es:10259/10648 2025-07-03 02:05:33.516 Repositorio Institucional de la Universidad de Burgos bubrep@ubu.es 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