title: Sox10 Regulates Stem/Progenitor and Mesenchymal Cell States in Mammary Epithelial Cells.
abstract: To discover mechanisms that mediate plasticity in mammary cells, we characterized signaling networks that are present in the mammary stem cells responsible for fetal and adult mammary development. These analyses identified a signaling axis between FGF signaling and the transcription factor Sox10. Here, we show that Sox10 is specifically expressed in mammary cells exhibiting the highest levels of stem/progenitor activity. This includes fetal and adult mammary cells in vivo and mammary organoids in vitro. Sox10 is functionally relevant, as its deletion reduces stem/progenitor competence whereas its overexpression increases stem/progenitor activity. Intriguingly, we also show that Sox10 overexpression causes mammary cells to undergo a mesenchymal transition. Consistent with these findings, Sox10 is preferentially expressed in stem- and mesenchymal-like breast cancers. These results demonstrate a signaling mechanism through which stem and mesenchymal states are acquired in mammary cells and suggest therapeutic avenues in breast cancers for which targeted therapies are currently unavailable.
authors.affiliation: Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Dravis
authors.affiliation: Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Benjamin T
authors.initials: BT
authors.lastname: Spike
authors.affiliation: Department of Pathology, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: J Chuck
authors.initials: JC
authors.lastname: Harrell
authors.affiliation: Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Claire
authors.initials: C
authors.lastname: Johns
authors.affiliation: Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Christy L
authors.initials: CL
authors.lastname: Trejo
authors.affiliation: Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: E Michelle
authors.initials: EM
authors.lastname: Southard-Smith
authors.affiliation: Departments of Genetics and Pathology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Perou
authors.affiliation: Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA. Electronic address: wahl@salk.edu.
authors.forename: Geoffrey M
authors.initials: GM
authors.lastname: Wahl
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D004847:Epithelial Cells; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D005333:Fetus; D005346:Fibroblast Growth Factors / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008321:Mammary Glands, Animal / Q000166:cytology / Q000378:metabolism; D042361:Mammary Glands, Human / Q000378:metabolism / Q000473:pathology; D059630:Mesenchymal Stem Cells; D051379:Mice; D055757:SOXE Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D018874:Spheroids, Cellular / Q000166:cytology / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D055757:SOXE Transcription Factors; C527924:Sox10 protein, mouse; D005346:Fibroblast Growth Factors