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Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis
Published on: January 31, 2025
Hedgehog/Gli promotes epithelial-mesenchymal transition in lung squamous cell carcinomas
Dongsheng Yue, Hui Li, Juanjuan Che
1Department of Lung Cancer, Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China. yuedongsheng_cg@163.com.
Background:
Squamous cell carcinomas (SCC) account for approximately 30% of non-small cell lung cancer. Investigation of the mechanism of invasion and metastasis of lung SCC will be of great help for the development of meaningful targeted therapeutics. This study is intended to understand whether the activation of Hedgehog (Hh) pathway is involved in lung SCC, and whether activated Hh signaling regulates metastasis through epithelial-mesenchymal transition (EMT) in lung SCC.
Methods:
Two cohorts of patients with lung SCC were studied. Protein expression was examined by immunohistochemistry, Western blot, or immunofluorescence. Protein expression levels in tissue specimens were scored and correlations were analyzed. Vismodegib and a Gli inhibitor were used to inhibit Shh/Gli activity, and recombinant Shh proteins were used to stimulate the Hh pathway in lung SCC cell lines. Cell migration assay was performed in vitro.
Results:
Shh/Gli pathway components were aberrantly expressed in lung SCC tissue samples. Gli1 expression was reversely associated with the expression of EMT markers E-Cadherin and β-Catenin in lung SCC specimens. Inhibition of the Shh/Gli pathway suppressed migration and up-regulated E-Cadherin expression in lung SCC cells. Stimulation of the pathway increased migration and down-regulated E-Cadherin expression in lung SCC cells.
Conclusions:
Our results suggested that the Shh/Gli pathway may be critical for lung SCC recurrence, metastasis and resistance to chemotherapy. Inhibition of the Shh/Gli pathway activity/function is a potential therapeutic strategy for the treatment of lung SCC patients.
Insights
The Hedgehog (Hh) pathway is implicated in lung squamous cell carcinoma (SCC) metastasis. Inhibiting Shh/Gli signaling may offer a therapeutic strategy for treating lung SCC by reducing cell migration and enhancing epithelial markers.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Lung squamous cell carcinoma (SCC) constitutes about 30% of non-small cell lung cancer.
- Understanding lung SCC invasion and metastasis mechanisms is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the involvement of the Hedgehog (Hh) pathway in lung SCC.
- To determine if activated Hh signaling drives metastasis via epithelial-mesenchymal transition (EMT) in lung SCC.
Main Methods:
- Analysis of Shh/Gli pathway components and EMT markers in lung SCC patient cohorts using immunohistochemistry, Western blot, and immunofluorescence.
- Inhibition of Shh/Gli activity with Vismodegib and Gli inhibitors, and stimulation with recombinant Shh proteins in lung SCC cell lines.
- In vitro cell migration assays to assess the impact of Shh/Gli pathway modulation on cell behavior.
Main Results:
- Aberrant expression of Shh/Gli pathway components was observed in lung SCC tissues.
- Gli1 expression inversely correlated with E-Cadherin and β-Catenin, key EMT markers.
- Shh/Gli pathway inhibition reduced cell migration and increased E-Cadherin, while pathway stimulation promoted migration and decreased E-Cadherin.
Conclusions:
- The Shh/Gli pathway plays a significant role in lung SCC recurrence, metastasis, and chemoresistance.
- Inhibiting Shh/Gli pathway activity presents a promising therapeutic approach for lung SCC patients.
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