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Updated: Dec 5, 2025
Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
Silencing SIX1 inhibits epithelial mesenchymal transition through regulating TGF-β/Smad2/3 signaling pathway in
1Department of Nuclear Medicine, The First People's Hospital of Jingzhou City, The First Affiliated Hospital of Yangtze University, Jingzhou 434000, Hubei Province, China.
Objective:
To investigate the sineoculis homeobox homolog 1 (SIX1) affect the epithelial mesenchymal transition (EMT) in papillary thyroid carcinoma (PTC) through regulating TGF-β/Smad2/3 signaling pathway.
Methods:
The SIX1 expression in cytological specimens, tissues or PTC cell lines was detected by qRT-PCR, western blotting or immunohistochemistry. A series of vitro experiments including flow cytometry, CCK-8, wound-healing and Transwell were used to evaluate the biological characteristics in a PTC cell line (NPA cells), which were divided into Blank, Negative control (NC), SIX1, SIX1-siRNA, LY-364947 (TGF-β/Smad2/3 pathway inhibitor) and SIX1 + LY-364947 groups. TGF-β/Smad2/3 pathway and EMT related protein expression were measured by qRT-PCR and western blotting.
Results:
SIX1 mRNA expression was increased in cytological specimens from PTC patients as compared with the non-toxic nodular goitre (NTG) patients. Moreover, compared with adjacent normal tissues, expressions of SIX1, N-cadherin and Vimentin were higher while E-cadherin was lower in PTC tissues; and SIX1 was positively correlated with N-cadherin and Vimentin but was negatively correlated with E-cadherin. Furthermore, the SIX1 expression was associated with histopathology, extrathyroidal extension (ETE), lymph node metastasis (LNM), pT stage, TNM stage, and distant metastasis. In addition, the expressions of TGFβ1, p-SMAD2/3, N-cadherin and Vimentin were downregulated in NPA cells after LY-364947 treatment with upregulated E-cadherin, decreased cell proliferation and metastasis, and enhanced cell apoptosis, which was reversed by SIX1 overexpression.
Conclusion:
Silencing SIX1 can inhibit TGF-β/Smad2/3 pathway, thereby suppressing EMT in PTC, which may be a novel avenue for the treatment of PTC.
Insights
Silencing SIX1 inhibits epithelial mesenchymal transition (EMT) in papillary thyroid carcinoma (PTC) by regulating the TGF-β/Smad2/3 pathway. This finding offers a potential new treatment strategy for PTC patients.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer.
- Epithelial mesenchymal transition (EMT) is a crucial process in cancer progression and metastasis.
- The role of sineoculis homeobox homolog 1 (SIX1) in PTC-associated EMT requires further elucidation.
Purpose of the Study:
- To investigate the effect of SIX1 on EMT in PTC.
- To explore the regulatory role of SIX1 in the TGF-β/Smad2/3 signaling pathway.
- To assess SIX1 as a potential therapeutic target for PTC.
Main Methods:
- SIX1 expression was analyzed in PTC patient samples and cell lines using qRT-PCR, western blotting, and immunohistochemistry.
- In vitro experiments evaluated cellular characteristics (proliferation, migration, invasion) in PTC cells with SIX1 manipulation and TGF-β/Smad2/3 pathway inhibition.
- Key pathway and EMT markers were quantified via qRT-PCR and western blotting.
Main Results:
- SIX1 expression was elevated in PTC tissues and correlated with advanced tumor features (ETE, LNM, metastasis).
- SIX1 overexpression promoted EMT markers (N-cadherin, Vimentin) and inhibited E-cadherin.
- Inhibition of the TGF-β/Smad2/3 pathway suppressed PTC cell proliferation and metastasis, effects reversed by SIX1 overexpression.
Conclusions:
- SIX1 promotes EMT in PTC by activating the TGF-β/Smad2/3 pathway.
- Silencing SIX1 can inhibit EMT and may serve as a therapeutic strategy for PTC.
- Targeting SIX1 offers a novel approach for PTC treatment.
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