Sox10 Regulates Stem/Progenitor and Mesenchymal Cell States in Mammary Epithelial Cells.

Dravis C, Spike BT, Harrell JC, Johns C, Trejo CL, Southard-Smith EM, Perou CM, Wahl GM
Cell Rep. 2015 12 (12): 2035-48

PMID: 26365194 · PMCID: PMC4591253 · DOI:10.1016/j.celrep.2015.08.040

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.

Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

MeSH Terms (20)

Animals Breast Neoplasms Cell Culture Techniques Cell Differentiation Epithelial-Mesenchymal Transition Epithelial Cells Female Fetus Fibroblast Growth Factors Gene Expression Regulation, Developmental Gene Expression Regulation, Neoplastic Humans Mammary Glands, Animal Mammary Glands, Human Mesenchymal Stem Cells Mice Signal Transduction SOXE Transcription Factors Spheroids, Cellular Tumor Cells, Cultured

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