Distinct EMT programs control normal mammary stem cells and tumour-initiating cells

Area of Science:

• Cancer Biology
• Stem Cell Research
• Molecular Oncology

Background:

• Tumour-initiating cells (TICs) drive cancer metastasis and relapse.
• TICs are hypothesized to arise from activated normal tissue stem cells.
• The transcription factor Slug regulates normal mammary stem cell activity.

Purpose of the Study:

• To investigate the molecular mechanisms underlying TIC generation.
• To compare the stem cell programs of normal mammary stem cells and TICs.
• To elucidate the roles of Slug and Snail in distinct stem cell populations.

Main Methods:

• Utilized genetically engineered knock-in reporter mouse lines.
• Analyzed mammary stem cells from the basal layer and TICs from the luminal layer.
• Investigated the expression and function of Slug and Snail EMT-TFs.

Main Results:

• Normal mammary stem cells use Slug, while breast TICs use Snail.
• These paralogous transcription factors induce distinct epithelial-to-mesenchymal transition (EMT) programs.
• Demonstrated differential utilization of EMT programs in normal versus cancer stem cells.

Conclusions:

• The stem cell programs in TICs and normal stem cells are not identical.
• Slug and Snail orchestrate distinct EMT programs in different mammary cell populations.
• Findings highlight key molecular differences relevant to cancer progression and normal tissue homeostasis.