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Epigenetic and Transcriptomic Profiling of Mammary Gland Development and Tumor Models Disclose Regulators of Cell State Plasticity.

Cancer cell | 2018

Cell state reprogramming during tumor progression complicates accurate diagnosis, compromises therapeutic effectiveness, and fuels metastatic dissemination. We used chromatin accessibility assays and transcriptional profiling during mammary development as an agnostic approach to identify factors that mediate cancer cell state interconversions. We show that fetal and adult basal cells share epigenetic features consistent with multi-lineage differentiation potential. We find that DNA-binding motifs for SOX transcription factors are enriched in chromatin that is accessible in stem/progenitor cells and inaccessible in differentiated cells. In both mouse and human tumors, SOX10 expression correlates with stem/progenitor identity, dedifferentiation, and invasive characteristics. Strikingly, we demonstrate that SOX10 binds to genes that regulate neural crest cell identity, and that SOX10-positive tumor cells exhibit neural crest cell features.

Pubmed ID: 30174241 RIS Download

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Associated grants

  • Agency: NCI NIH HHS, United States
    Id: R01 CA186043
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM007752
  • Agency: NCI NIH HHS, United States
    Id: F31 CA206416
  • Agency: NCI NIH HHS, United States
    Id: F32 CA174430
  • Agency: NCI NIH HHS, United States
    Id: R35 CA197687
  • Agency: NCI NIH HHS, United States
    Id: R35 CA197699
  • Agency: NCI NIH HHS, United States
    Id: P30 CA014195

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SAMTOOLS (software resource)

RRID:SCR_002105

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RRID:SCR_005476

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RRID:SCR_003032

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RRID:SCR_001905

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