2026-06-27T23:19:27Zhttps://docta.ucm.es/rest/oai/request

oai:docta.ucm.es:20.500.14352/79932025-08-28T13:45:11Zcom_20.500.14352_14col_20.500.14352_15

00925njm 22002777a 4500 dc Blanco Gómez, Adrián author Hontecillas Prieto, Lourdes author Corchado Cobos, Roberto author García Sancha, Natalia author Salvador Tormo, Nélida author Castellanos Martín, Andrés author Sáez Freire, María del Mar author Mendiburu-Eliçabe Garganta, Marina author Alonso López, Diego author De Las Rivas Sanz, Javier author Lorente Pérez, María Del Mar author García Casas, Ana author Del Carmen Martínez, Sofía author Abad Hernández, María Del Mar author Cruz Hernández, Juan Jesús author Rodríguez Sánchez, César Augusto author Claros Ampuero, Juncal author García Cenador, Begoña author García Criado, Javier author Orimo, Akira author Gridley, Thomas author Pérez Losada, Jesús author Castillo Lluva, Sonia author 2020 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. 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-20-0278. 0008-5472 10.1158/0008-5472.CAN-20-0278 https://hdl.handle.net/20.500.14352/7993 https://doi.org/10.1158/0008-5472.CAN-20-0278 Stromal SNAI2 is required for ERBB2 breast cancer progression