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Updated: Apr 11, 2026
Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
CrkL meditates CCL20/CCR6-induced EMT in gastric cancer
Gang Han1, Dawei Wu2, Yongan Yang2
1Department of General Surgery, Affiliated Hospital of Shandong Academy of Medical Sciences, Jinan, Shandong, China.
Background:
In recent years, Crk-like adapter protein (CrkL) has been identified as a key regulator in the epithelial-to-mesenchymal transition (EMT). However, the molecular mechanisms underlying the CC chemokine receptor 6 (CCR6) and chemokine (C-C motif) ligand 20 (CCL20)-induced EMT in gastric cancer are still unclear.
Methods:
We conducted the immunohistochemistry and immunoblotting to detect the expression of CCR6 and CrkL in 90 cases of gastric cancer tissues and five kinds of cell lines. And then, gastric cancer cells were subjected to small interfering RNA (siRNA) treatment and in vitro assay.
Results:
Both CCR6 and CrkL were aberrantly expressed in gastric cancer specimens and closely correlated with differentiation of cell lines. The expression of CCR6 and CrkL was also significantly associated with metastasis, stage, and poor prognosis of gastric cancer. In addition, we validated CCL20 activated the expression of p-CrkL, p-Erk1/2, p-Akt, vimentin, N-cadherin and MMP2 in MGC803 cells in a dose-dependent manner. However, si-CrkL abrogated the CCL20-induced p-Erk1/2, vimentin, N-cadherin and MMP2 expression. Most importantly, the knockdown of CrkL decreased migration and invasion of MGC803 cells.
Conclusions:
CrkL mediates CCL20/CCR6-induced EMT via Akt pathway, instead of Erk1/2 pathway in development of gastric cancer, which indicated CCL20/CCR6-CrkL-Erk1/2-EMT pathway may be targeted to antagonize the progression of gastric cancer.
Insights
Crk-like adapter protein (CrkL) drives gastric cancer progression by mediating CCL20/CCR6-induced epithelial-mesenchymal transition (EMT) through the Akt pathway. Targeting this CCL20/CCR6-CrkL-EMT axis offers a potential therapeutic strategy.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Crk-like adapter protein (CrkL) is a key regulator of epithelial-to-mesenchymal transition (EMT).
- The precise mechanisms of CC chemokine receptor 6 (CCR6) and chemokine (C-C motif) ligand 20 (CCL20)-induced EMT in gastric cancer remain incompletely understood.
Purpose of the Study:
- To elucidate the role of CrkL in CCL20/CCR6-mediated EMT in gastric cancer.
- To investigate the underlying molecular pathways involved in this process.
Main Methods:
- Immunohistochemistry and immunoblotting were used to assess CCR6 and CrkL expression in 90 gastric cancer tissues and five cell lines.
- Gastric cancer cells underwent small interfering RNA (siRNA) treatment and in vitro assays to evaluate functional impacts.
Main Results:
- Aberrant expression of CCR6 and CrkL was observed in gastric cancer, correlating with poor prognosis, metastasis, and advanced stage.
- CCL20 stimulation upregulated p-CrkL, p-Akt, and EMT markers (vimentin, N-cadherin, MMP2) in MGC803 cells, an effect abrogated by si-CrkL.
- Knockdown of CrkL significantly reduced MGC803 cell migration and invasion.
Conclusions:
- CrkL mediates CCL20/CCR6-induced EMT in gastric cancer predominantly via the Akt pathway, not the Erk1/2 pathway.
- The CCL20/CCR6-CrkL-Akt-EMT pathway represents a potential therapeutic target for antagonizing gastric cancer progression.
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