دورية أكاديمية
Stromal SNAI2 is required for ERBB2 breast cancer progression
| العنوان: | Stromal SNAI2 is required for ERBB2 breast cancer progression |
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| المؤلفون: | Blanco Gómez, Adrián, Hontecillas Prieto, Lourdes, Corchado Cobos, Roberto, García Sancha, Natalia, Salvador Tormo, Nélida, Castellanos Martín, Andrés, Sáez Freire, María del Mar, Mendiburu Elicabe, Marina, Alonso López, Diego, De Las Rivas Sanz, Javier, Lorente Pérez, María Del Mar, García Casas, Ana, Del Carmen Martínez, Sofía, Abad Hernández, María del Mar, Cruz Hernández, Juan Jesús, Rodríguez Sánchez, César Augusto, Claros Ampuero, Juncal, García Cenador, Begoña, García Criado, Javier, Orimo, Akira, Gridley, Thomas, Pérez Losada, Jesús, Castillo Lluva, Sonia |
| بيانات النشر: | American Association of Cancer Research |
| سنة النشر: | 2020 |
| المجموعة: | Universidad Complutense de Madrid (UCM): E-Prints Complutense |
| مصطلحات موضوعية: | 575:61, 618.19-006.04, Breast cancer, Stromal cells, Genética médica, Oncología, Biología molecular (Biología), 2410.07 Genética Humana, 3201.01 Oncología, 2415 Biología Molecular |
| الوصف: | SNAI2 overexpression appears to be associated with poor prognosis in breast cancer, yet it remains unclear in which breast cancer subtypes this occurs. Here we show that excess SNAI2 is associated with a poor prognosis of luminal B HER2+/ERBB2+ breast cancers in which SNAI2 expression in the stroma but not the epithelium correlates with tumor proliferation. To determine how stromal SNAI2 might influence HER2+ tumor behavior, Snai2-deficient mice were crossed with a mouse line carrying the ErbB2/Neu protooncogene to generate HER2+/ERBB2+ breast cancer. Tumors generated in this model expressed SNAI2 in the stroma but not the epithelium, allowing for the role of stromal SNAI2 to be studied without interference from the epithelial compartment. The absence of SNAI2 in the stroma of HER2+/ERBB2+ tumors is associated with: (i) lower levels of cyclin D1 (CCND1) and reduced tumor epithelium proliferation; (ii) higher levels of AKT and a lower incidence of metastasis; (iii) lower levels of angiopoietin-2 (ANGPT2), and more necrosis. Together, these results indicate that the loss of SNAI2 in cancer-associated fibroblasts limits the production of some cytokines, which influences AKT/ERK tumor signaling and subsequent proliferative and metastatic capacity of ERBB2+ breast cancer cells. Accordingly, SNAI2 expression in the stroma enhanced the tumorigenicity of luminal B HER2+/ERBB2+ breast cancers. This work emphasizes the importance of stromal SNAI2 in breast cancer progression and patients' prognosis. ; Ministerio de Economía y Competitividad (España) ; Instituto de Salud Carlos III ; Junta de Castilla y León ; National Institutes of Health ; Sandra Ibarra Foundation for Solidarity against Cancer ; “We can be heroes” Foundation ; Federación Española de Enfermedades Raras ; Sección Deptal. de Bioquímica y Biología Molecular (Biológicas) ; Depto. de Bioquímica y Biología Molecular ; Fac. de Ciencias Biológicas ; Fac. de Ciencias Químicas ; TRUE ; pub |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0008-5472 |
| العلاقة: | info:eu-repo/grantAgreement/MINECO/SAF2015-64499-R; info:eu-repo/grantAgreement/PIE14/00066; info:eu-repo/grantAgreement/CSI234P18; nfo:eu-repo/grantAgreement/R01HD034883; info:eu-repo/grantAgreement/MINECO/SAF2014-56989-R; info:eu-repo/grantAgreement/MINECO/SAF2017-88854R; https://hdl.handle.net/20.500.14352/7993Test; Blanco-Gómez A, Hontecillas-Prieto L, Corchado-Cobos R, García-Sancha N, Salvador N, Castellanos-Martín A, et al. Stromal SNAI2 Is Required for ERBB2 Breast Cancer Progression. Cancer Research 2020;80:5216–30. https://doi.org/10.1158/0008-5472.CAN-20-0278Test.; https://doi.org/10.1158/0008-5472.CAN-20-0278Test |
| DOI: | 10.1158/0008-5472.CAN-20-0278 |
| الإتاحة: | https://doi.org/20.500.14352/799310.1158/0008-5472.CAN-20-0278Test https://hdl.handle.net/20.500.14352/7993Test |
| حقوق: | restricted access |
| رقم الانضمام: | edsbas.F0A2FDC4 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 00085472 |
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| DOI: | 10.1158/0008-5472.CAN-20-0278 |