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Published on: October 27, 2020
[Effects of inhibition of Hedgehog signaling pathway for transforming growth factor-β-induced epithelial-mesenchymal
Jian-hui Chen1, Hui Wu, Jin-ping Ma
1Department of Gastrointestinal Surgery, First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
Objective:
To elucidate the mechanism of Hedgehog pathway in the metastasis of gastric cancer and examine particularly the effect on epithelial-mesenchymal transition (EMT).
Methods:
Using pharmacological and siRNA knockdown approach, the Hedgehog pathway was inhibited. The cellular morphology, protein level, invasion and metastatic abilities were measured by microscope, Western blot, Transwell invasion assay and Transwell migration assay.
Results:
Under the inhibition of Hedgehog pathway, the invasive and migration abilities of gastric cancer decreased. The transforming growth factor (TGF) -β could induce spindle-like-shaped morphological changes with a down-regulation of epithelial characteristic (decreased E-cadherin protein level) and an up-regulation of mesenchymal characteristics (increased Vimentin protein level). There were concurrent increases of invasive and migration potentials by 3 and 4 folds respectively.However, under the continuous stimulation of TGF-β, the inhibition of Hedgehog pathway could reverse the EMT changes, lower the expression of vimentin and reduce the invasion and metastatic abilities by 3 and 2 folds respectively.
Conclusions:
The inhibition of Hedgehog pathway can decrease the TGF-β-inducing EMT.It suggests that Hedgehog pathway may play a critical role in the metastasis of gastric cancer.
Insights
Inhibiting the Hedgehog pathway reduces gastric cancer metastasis by reversing transforming growth factor-beta (TGF-β)-induced epithelial-mesenchymal transition (EMT). This highlights the pathway
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Context:
- Gastric cancer is a leading cause of cancer-related deaths worldwide.
- Metastasis significantly contributes to poor prognosis in gastric cancer.
- The Hedgehog signaling pathway is implicated in various cancers, but its role in gastric cancer metastasis requires further elucidation.
Purpose:
- To investigate the role of the Hedgehog signaling pathway in gastric cancer metastasis.
- To examine the specific effect of Hedgehog pathway inhibition on epithelial-mesenchymal transition (EMT).
Summary:
- Pharmacological and siRNA inhibition of the Hedgehog pathway reduced gastric cancer cell invasion and migration.
- Transforming growth factor-beta (TGF-β) induced EMT, characterized by altered E-cadherin and Vimentin levels, increasing invasion and migration.
- Hedgehog pathway inhibition reversed TGF-β-induced EMT, decreasing Vimentin expression and reducing metastatic potential.
Impact:
- Findings suggest the Hedgehog pathway is a critical regulator of gastric cancer metastasis.
- Inhibiting the Hedgehog pathway presents a potential therapeutic strategy to combat gastric cancer spread.
- This study provides mechanistic insights into EMT regulation in gastric cancer.
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