title: Heterogeneity between triple negative breast cancer cells due to differential activation of Wnt and PI3K/AKT pathways.
abstract: The lack of a successful treatment for triple-negative breast cancer demands the study of the heterogeneity of cells that constitute these tumors. With this aim, two clones from triple negative breast MDA-MB-231 cancer cells were isolated: One with fibroblast-like appearance (F) and another with semi-epithelial (SE) morphology. Cells of the F clone have a higher migration and tumorigenesis capacity than SE cells, suggesting that these cells are in a more advanced stage of epithelial to mesenchymal transformation. In agreement, F cells have a diminished expression of the tight junction proteins claudins 1 and 4, and an increased content of β-catenin. The latter is due to an augmented activity of the canonical Wnt route and of the EGFR/PI3K/mTORC2/AKT pathway favoring the cytoplasmic accumulation of β-catenin and its transcriptional activity. In addition, F cells display increased phosphorylation of β-catenin at Tyr654 by Src. These changes favor in F cells, the over-expression of Snail that promotes EMT. Finally, we observe that both F and SE cells display markers of cancer stem cells, which are more abundant in the F clone.
authors.affiliation: Department of Physiology, Biophysics and Neuroscience, Center for Research and Advanced Studies (CINVESTAV), México D.F., Mexico.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Martínez-Revollar
authors.affiliation: National Laboratories of Genomics for Biodiversity, Center for Research and Advanced Studies (CINVESTAV), Irapuato, Mexico.
authors.forename: Erika
authors.initials: E
authors.lastname: Garay
authors.affiliation: Department of Physiology, Biophysics and Neuroscience, Center for Research and Advanced Studies (CINVESTAV), México D.F., Mexico.
authors.forename: Dolores
authors.initials: D
authors.lastname: Martin-Tapia
authors.affiliation: Department of Physiology, Biophysics and Neuroscience, Center for Research and Advanced Studies (CINVESTAV), México D.F., Mexico.
authors.forename: Porfirio
authors.initials: P
authors.lastname: Nava
authors.affiliation: Department of Biotechnology, Instituto Tecnológico de Monterrey (ITESM), Campus Puebla, Mexico.
authors.forename: Miriam
authors.initials: M
authors.lastname: Huerta
authors.affiliation: Department of Toxicology, Center for Research and Advanced Studies (CINVESTAV), México D.F., Mexico.
authors.forename: Esther
authors.initials: E
authors.lastname: Lopez-Bayghen
authors.affiliation: Faculty of Medicine, UNAM, Mexico D.F., Mexico; National Institute of Genomic Medicine, Mexico D.F., Mexico.
authors.forename: Noemí
authors.initials: N
authors.lastname: Meraz-Cruz
authors.affiliation: Department of Physiology, Biophysics and Neuroscience, Center for Research and Advanced Studies (CINVESTAV), México D.F., Mexico.
authors.forename: José
authors.initials: J
authors.lastname: Segovia
authors.affiliation: Department of Physiology, Biophysics and Neuroscience, Center for Research and Advanced Studies (CINVESTAV), México D.F., Mexico. Electronic address: lorenza@fisio.cinvestav.mx.
authors.forename: Lorenza
authors.initials: L
authors.lastname: González-Mariscal
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D002633:Chemotaxis; D058750:Epithelial-Mesenchymal Transition; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D000076225:Mechanistic Target of Rapamycin Complex 2; D051379:Mice; D008819:Mice, Nude; D046912:Multiprotein Complexes / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured; D051153:Wnt Proteins / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D066246:ErbB Receptors; D000076225:Mechanistic Target of Rapamycin Complex 2; D046912:Multiprotein Complexes; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D051153:Wnt Proteins; D051176:beta Catenin; C512478:EGFR protein, human
keywords: AKT; Cancer cells heterogeneity; Triple negative breast cancer; Wnt; β-catenin