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Updated: Jan 24, 2026

Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
Disulfiram inhibits epithelial-mesenchymal transition through TGFβ-ERK-Snail pathway independently of Smad4 to
Wenhuan Bu1, Zilin Wang1, Lin Meng1
1Department of Oral Pathology, School and Hospital of Stomatology, Jilin University, 130000 Changchun, People's Republic of China.
Abstract:
Purpose: Smad4 loss is highly related to poor prognosis and decreased patient survival in oral squamous cell carcinoma (OSCC), suggesting that agents that target both Smad4-mutated and Smad4 wild-type cells could treat OSCC more effectively. Disulfiram (Dsf) has anticancer activity through a variety of mechanisms, including inhibition of epithelial-mesenchymal transition (EMT). It remains unclear whether Dsf has the same effect on Smad4-mutated and Smad4 wild-type OSCC or not and what mechanism is involved. Methods: Effect of Dsf on TGFβ1-induced EMT in CAL27 (Smad4 mutation) and SCC25 (Smad4 wild-type) cells were evaluated through analyzing changes in morphology, expression of EMT markers, and migration and invasion of cells. The ERK-pathway inhibitor U0126 was used to confirm TGFβ-ERK-Snail pathway-mediated cell behavior. Dsf's effects on tumor growth and metastasis in vivo were examined through a subcutaneous xenograft mouse model and an intravenous tumor mouse model. Results: Dsf inhibited TGFβ1-induced EMT through suppression of morphological change, EMT-marker expression, and cell migration and invasion in both CAL27 and SCC25. Phosphorylation of ERK and expression of Snail were blocked by Dsf treatment. Like Dsf, U0126 had a similar effect on EMT of CAL27 and SCC25. Dsf also reduced tumor growth and metastasis in vivo, accompanied by decreased expression of EMT markers in tumors. Conclusion: These results indicated that Dsf inhibited EMT of OSCC in vitro and in vivo independently of Smad4 through suppression of the TGFβ-ERK-Snail pathway, suggesting the broad-spectrum anticancer potential of Dsf for clinical use against OSCC.
Insights
Disulfiram (Dsf) effectively inhibits epithelial-mesenchymal transition (EMT) in oral squamous cell carcinoma (OSCC) cells, regardless of Smad4 mutation status. This suggests Dsf
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Smad4 loss is linked to poor prognosis in oral squamous cell carcinoma (OSCC).
- Disulfiram (Dsf) exhibits anticancer properties, including the inhibition of epithelial-mesenchymal transition (EMT).
- The effect of Dsf on Smad4-mutated versus wild-type OSCC and its underlying mechanisms require clarification.
Purpose of the Study:
- To investigate the efficacy of Disulfiram (Dsf) in inhibiting TGFβ1-induced epithelial-mesenchymal transition (EMT) in both Smad4-mutated and Smad4 wild-type oral squamous cell carcinoma (OSCC) cells.
- To elucidate the molecular mechanisms by which Dsf affects EMT, focusing on the TGFβ-ERK-Snail pathway.
- To evaluate the in vivo therapeutic potential of Dsf against OSCC tumor growth and metastasis.
Main Methods:
- Assessed Dsf's impact on TGFβ1-induced EMT in CAL27 (Smad4 mutation) and SCC25 (Smad4 wild-type) OSCC cells by analyzing morphology, EMT markers, migration, and invasion.
- Utilized the ERK-pathway inhibitor U0126 to confirm the involvement of the TGFβ-ERK-Snail pathway.
- Examined Dsf's effects on tumor growth and metastasis in vivo using subcutaneous xenograft and intravenous tumor mouse models.
Main Results:
- Dsf suppressed TGFβ1-induced EMT, including morphological changes, EMT marker expression, and cell migration/invasion, in both CAL27 and SCC25 cells.
- Dsf treatment blocked ERK phosphorylation and Snail expression, indicating inhibition of the TGFβ-ERK-Snail pathway.
- In vivo studies showed Dsf reduced tumor growth and metastasis, with decreased EMT marker expression in tumors.
Conclusions:
- Disulfiram (Dsf) inhibits EMT in oral squamous cell carcinoma (OSCC) both in vitro and in vivo, independent of Smad4 status.
- The mechanism involves the suppression of the TGFβ-ERK-Snail pathway.
- Dsf demonstrates broad-spectrum anticancer potential for clinical application in OSCC treatment.
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