Biomaterial Database

Stromal SNAI2 Is Required for ERBB2 Breast Cancer Progression. 2020

Adrián Blanco-Gómez, and Lourdes Hontecillas-Prieto, and Roberto Corchado-Cobos, and Natalia García-Sancha, and Nélida Salvador, and Andrés Castellanos-Martín, and María Del Mar Sáez-Freire, and Marina Mendiburu-Eliçabe, and Diego Alonso-López, and Javier De Las Rivas, and Mar Lorente, and Ana García-Casas, and Sofía Del Carmen, and María Del Mar Abad-Hernández, and Juan Jesús Cruz-Hernández, and César Augusto Rodríguez-Sánchez, and Juncal Claros-Ampuero, and Begoña García-Cenador, and Javier García-Criado, and Akira Orimo, and Thomas Gridley, and Jesús Pérez-Losada, and Sonia Castillo-Lluva

Instituto de Biología Molecular y Celular del Cáncer (IBMCC-CIC), Universidad de Salamanca/CSIC, Salamanca, Spain.

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. SIGNIFICANCE: Stromal SNAI2 expression enhances the tumorigenicity of luminal B HER2+ breast cancers and can identify a subset of patients with poor prognosis, making SNAI2 a potential therapeutic target for this disease. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/23/5216/F1.large.jpg.

UI	MeSH Term	Description	Entries
D001943	Breast Neoplasms	Tumors or cancer of the human BREAST.	Breast Cancer,Breast Tumors,Cancer of Breast,Breast Carcinoma,Cancer of the Breast,Human Mammary Carcinoma,Malignant Neoplasm of Breast,Malignant Tumor of Breast,Mammary Cancer,Mammary Carcinoma, Human,Mammary Neoplasm, Human,Mammary Neoplasms, Human,Neoplasms, Breast,Tumors, Breast,Breast Carcinomas,Breast Malignant Neoplasm,Breast Malignant Neoplasms,Breast Malignant Tumor,Breast Malignant Tumors,Breast Neoplasm,Breast Tumor,Cancer, Breast,Cancer, Mammary,Cancers, Mammary,Carcinoma, Breast,Carcinoma, Human Mammary,Carcinomas, Breast,Carcinomas, Human Mammary,Human Mammary Carcinomas,Human Mammary Neoplasm,Human Mammary Neoplasms,Mammary Cancers,Mammary Carcinomas, Human,Neoplasm, Breast,Neoplasm, Human Mammary,Neoplasms, Human Mammary,Tumor, Breast
D002465	Cell Movement	The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.	Cell Migration,Locomotion, Cell,Migration, Cell,Motility, Cell,Movement, Cell,Cell Locomotion,Cell Motility,Cell Movements,Movements, Cell
D005260	Female		Females
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000071250	Snail Family Transcription Factors	A transcription factor family characterized by the presence of several C-terminal CYS2-HIS2 ZINC FINGERS. They function in many developmental processes including the induction of the EPITHELIAL-MESENCHYMAL TRANSITION; maintenance of embryonic MESODERM; growth arrest, CELL SURVIVAL; and CELL MIGRATION.	Slug Transcription Factors,Snail Transcription Factors,Transcription Factors, Slug,Transcription Factors, Snail
D000072645	Cancer-Associated Fibroblasts	Subpopulation of heterogeneous fibroblasts within the TUMOR MICROENVIRONMENT that support NEOPLASTIC CELL TRANSFORMATION and NEOPLASTIC PROCESSES.	Cancer Associated Fibroblasts,Tumor-Associated Fibroblasts,Cancer Associated Fibroblast,Cancer-Associated Fibroblast,Fibroblast, Cancer Associated,Fibroblast, Cancer-Associated,Fibroblast, Tumor-Associated,Fibroblasts, Cancer Associated,Fibroblasts, Cancer-Associated,Fibroblasts, Tumor-Associated,Tumor Associated Fibroblasts,Tumor-Associated Fibroblast
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D015972	Gene Expression Regulation, Neoplastic	Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.	Neoplastic Gene Expression Regulation,Regulation of Gene Expression, Neoplastic,Regulation, Gene Expression, Neoplastic
D017154	Stromal Cells	Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere.	Cell, Stromal,Cells, Stromal,Stromal Cell
D045744	Cell Line, Tumor	A cell line derived from cultured tumor cells.	Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines