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Related Experiment Video

Updated: Feb 20, 2026

Isolation and Functional Assessment of Human Breast Cancer Stem Cells from Cell and Tissue Samples
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Embryonic stem cell secreted factors decrease invasiveness of triple-negative breast cancer cells through regulome

Elizabeth Tarasewicz1, Robert S Oakes2, Misael O Aviles3

  • 1a Department of Surgery , Northwestern University Feinberg School of Medicine , Chicago , IL , USA.

Cancer Biology & Therapy
|October 21, 2017
PubMed
Summary
This summary is machine-generated.

Mouse embryonic stem cell conditioned media (mESC CM) reprogrammed triple-negative breast cancer (TNBC) cells to a less aggressive state. TRanscriptional Activity CEll aRray (TRACER) identified key transcription factors involved in this beneficial phenotype transition.

Keywords:
breast cancercancer stem cellembryonic stem cellepithelial-mesenchymal transitionmetastasismicroenvironmenttranscription factors

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Area of Science:

  • Oncology
  • Stem Cell Biology
  • Molecular Biology

Background:

  • Stem cell microenvironments can reduce cancer cell invasiveness.
  • Understanding disease regression mechanisms is crucial for developing targeted therapies for aggressive cancers.

Purpose of the Study:

  • To investigate the reprogramming of triple-negative breast cancer (TNBC) cells towards a less aggressive phenotype using mouse embryonic stem cell conditioned media (mESC CM).
  • To elucidate the mechanisms, particularly transcription factor (TF) activity, underlying this phenotypic transition using TRanscriptional Activity CEll aRray (TRACER).

Main Methods:

  • TNBC cells were exposed to mESC CM to induce a less aggressive phenotype.
  • Carcinogenic phenotypes (proliferation, invasion, migration, stemness) were assessed.
  • Protein and gene expression of epithelial-mesenchymal transition (EMT) markers were analyzed.
  • TRACER technology was employed to quantify the activity of 11 TFs over 6 days.

Main Results:

  • mESC CM exposure decreased TNBC cell proliferation, invasion, migration, and stemness.
  • E-cadherin expression increased, while MMP9, fibronectin, vimentin, and Snail expression decreased.
  • TRACER identified decreased activity in 7 TFs (Smad3, NF-κΒ, MEF2, GATA, Hif1, Sp1, RXR) associated with reduced EMT.
  • Specific analysis revealed decreased noncanonical Smad3 phosphorylation and increased GATA3 expression/phosphorylation, leading to reduced cell migration.

Conclusions:

  • mESC CM effectively reduces the aggressiveness of TNBC cells by modulating EMT and TF activity.
  • TRACER is a valuable tool for dissecting TF dynamics during cancer cell reprogramming.
  • The study identified novel mechanistic links between the embryonic microenvironment, TF activity (Smad3, GATA3), and TNBC cell plasticity.