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Updated: May 17, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
Efficient TGFβ-induced epithelial-mesenchymal transition depends on hyaluronan synthase HAS2
1Ludwig Institute for Cancer Research, Science for life Laboratory, Biomedical Center, Uppsala University, Uppsala, Sweden.
Transforming growth factor β (TGFβ) stimulates hyaluronan synthase 2 (HAS2) to promote cancer cell migration and metastasis. HAS2, not extracellular hyaluronan, is crucial for TGFβ-induced epithelial-mesenchymal transition (EMT).
Area of Science:
- Cell Biology
- Cancer Research
- Molecular Biology
Background:
- Epithelial-mesenchymal transition (EMT) is a key process in cancer metastasis.
- Transforming growth factor β (TGFβ) is a known inducer of EMT.
Purpose of the Study:
- To investigate the role of hyaluronan synthesis in TGFβ-induced EMT.
- To determine the specific contribution of hyaluronan synthase 2 (HAS2) in this process.
Main Methods:
- Upregulation of HAS2 expression by TGFβ in NMuMG cells.
- Investigating TGFβ signaling pathways (Smad, p38 MAPK).
- Using siRNA to suppress HAS2 and assessing EMT markers (ZO-1, fibronectin, Snail1, Zeb1) and cell migration.
Main Results:
- TGFβ stimulates hyaluronan synthesis via HAS2 upregulation, dependent on TGFβ receptor type I, Smad, and p38 MAPK.
- HAS2 knockdown inhibited TGFβ-induced EMT by approximately 50% and decreased EMT marker expression.
- HAS2 suppression abolished TGFβ-induced cell migration, while CD44 inhibition did not.
Conclusions:
- TGFβ-dependent HAS2 expression is a critical regulator of TGFβ-induced EMT.
- Extracellular hyaluronan and CD44 engagement are not essential for TGFβ-induced EMT, but HAS2 is vital for cell migration.
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