Metadherin Regulates Inflammatory Breast Cancer Invasion and Metastasis. 2023

Gabriela Ortiz-Soto, and Natalia S Babilonia-Díaz, and Mercedes Y Lacourt-Ventura, and Delmarie M Rivera-Rodríguez, and Jailenne I Quiñones-Rodríguez, and Mónica Colón-Vargas, and Israel Almodóvar-Rivera, and Luis E Ferrer-Torres, and Ivette J Suárez-Arroyo, and Michelle M Martínez-Montemayor
Department of Biochemistry, Universidad Central del Caribe-School of Medicine, Bayamón, PR 00960, USA.

Inflammatory breast cancer (IBC) is one of the most lethal subtypes of breast cancer (BC), accounting for approximately 1-5% of all cases of BC. Challenges in IBC include accurate and early diagnosis and the development of effective targeted therapies. Our previous studies identified the overexpression of metadherin (MTDH) in the plasma membrane of IBC cells, further confirmed in patient tissues. MTDH has been found to play a role in signaling pathways related to cancer. However, its mechanism of action in the progression of IBC remains unknown. To evaluate the function of MTDH, SUM-149 and SUM-190 IBC cells were edited with CRISPR/Cas9 vectors for in vitro characterization studies and used in mouse IBC xenografts. Our results demonstrate that the absence of MTDH significantly reduces IBC cell migration, proliferation, tumor spheroid formation, and the expression of NF-κB and STAT3 signaling molecules, which are crucial oncogenic pathways in IBC. Furthermore, IBC xenografts showed significant differences in tumor growth patterns, and lung tissue revealed epithelial-like cells in 43% of wild-type (WT) compared to 29% of CRISPR xenografts. Our study emphasizes the role of MTDH as a potential therapeutic target for the progression of IBC.

UI MeSH Term Description Entries
D008565 Membrane Proteins Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. Cell Membrane Protein,Cell Membrane Proteins,Cell Surface Protein,Cell Surface Proteins,Integral Membrane Proteins,Membrane-Associated Protein,Surface Protein,Surface Proteins,Integral Membrane Protein,Membrane Protein,Membrane-Associated Proteins,Membrane Associated Protein,Membrane Associated Proteins,Membrane Protein, Cell,Membrane Protein, Integral,Membrane Proteins, Integral,Protein, Cell Membrane,Protein, Cell Surface,Protein, Integral Membrane,Protein, Membrane,Protein, Membrane-Associated,Protein, Surface,Proteins, Cell Membrane,Proteins, Cell Surface,Proteins, Integral Membrane,Proteins, Membrane,Proteins, Membrane-Associated,Proteins, Surface,Surface Protein, Cell
D009361 Neoplasm Invasiveness Ability of neoplasms to infiltrate and actively destroy surrounding tissue. Invasiveness, Neoplasm,Neoplasm Invasion,Invasion, Neoplasm
D009362 Neoplasm Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Metastase,Metastasis,Metastases, Neoplasm,Metastasis, Neoplasm,Neoplasm Metastases,Metastases
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
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
D015815 Cell Adhesion Molecules Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis. Cell Adhesion Molecule,Intercellular Adhesion Molecule,Intercellular Adhesion Molecules,Leukocyte Adhesion Molecule,Leukocyte Adhesion Molecules,Saccharide-Mediated Cell Adhesion Molecules,Saccharide Mediated Cell Adhesion Molecules,Adhesion Molecule, Cell,Adhesion Molecule, Intercellular,Adhesion Molecule, Leukocyte,Adhesion Molecules, Cell,Adhesion Molecules, Intercellular,Adhesion Molecules, Leukocyte,Molecule, Cell Adhesion,Molecule, Intercellular Adhesion,Molecule, Leukocyte Adhesion,Molecules, Cell Adhesion,Molecules, Intercellular Adhesion,Molecules, Leukocyte Adhesion
D016328 NF-kappa B Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA. Immunoglobulin Enhancer-Binding Protein,NF-kappa B Complex,Nuclear Factor kappa B,Transcription Factor NF-kB,kappa B Enhancer Binding Protein,Ig-EBP-1,NF-kB,NF-kappaB,Nuclear Factor-Kappab,Complex, NF-kappa B,Enhancer-Binding Protein, Immunoglobulin,Factor NF-kB, Transcription,Factor-Kappab, Nuclear,Ig EBP 1,Immunoglobulin Enhancer Binding Protein,NF kB,NF kappa B Complex,NF kappaB,NF-kB, Transcription Factor,Nuclear Factor Kappab,Transcription Factor NF kB
D016601 RNA-Binding Proteins Proteins that bind to RNA molecules. Included here are RIBONUCLEOPROTEINS and other proteins whose function is to bind specifically to RNA. Double-Stranded RNA-Binding Protein,Double-Stranded RNA-Binding Proteins,ds RNA-Binding Protein,RNA-Binding Protein,ds RNA-Binding Proteins,Double Stranded RNA Binding Protein,Double Stranded RNA Binding Proteins,Protein, Double-Stranded RNA-Binding,Protein, ds RNA-Binding,RNA Binding Protein,RNA Binding Proteins,RNA-Binding Protein, Double-Stranded,RNA-Binding Protein, ds,RNA-Binding Proteins, Double-Stranded,ds RNA Binding Protein
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
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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