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Updated: Aug 20, 2026

Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
RET signals through focal adhesion kinase in medullary thyroid cancer cells
Ganesh R Panta1, Fiemu Nwariaku, Lawrence T Kim
1Surgical Service 112, Central Arkansas Veterans Healthcare System, 4300 W. 7th Street, Little Rock, AR 72205, USA.
Background:
The RET proto-oncogene is implicated in medullary thyroid cancer (MTC) and has been shown to signal indirectly to focal adhesion kinase (FAK) in cell types other than MTC. We have previously shown that FAK is phosphorylated in MTC cells. We hypothesized that inhibition of RET with pharmacologic inhibitors or by depletion with siRNA would decrease FAK phosphorylation in MTC cells, thereby implicating a RET-FAK signaling pathway.
Methods:
Human MTC cells (TT cells) were treated with pharmacologic inhibitors or transfected with RET siRNA. Total protein was detected by immunoblotting. Phosphorylated FAK was detected by immunoprecipitating total FAK and immunoblotting with antiphosphotyrosine.
Results:
Treatment of MTC cells with the inhibitor PP2 significantly inhibited RET phosphorylation and, to a lesser extent, FAK phosphorylation. Imatinib mesylate inhibited FAK phosphorylation only at high doses. RET siRNA significantly decreased RET expression and FAK phosphorylation.
Conclusions:
RET signals through FAK in MTC cells. Whether this is due to a direct or indirect interaction is not yet clear. PP2 or a similar inhibitor might be a useful treatment for MTC.
Insights
RET proto-oncogene inhibition decreases focal adhesion kinase phosphorylation in medullary thyroid cancer cells, suggesting a potential therapeutic target. Further research is needed to clarify the direct interaction.
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- The RET proto-oncogene plays a role in medullary thyroid cancer (MTC).
- Focal adhesion kinase (FAK) phosphorylation is observed in MTC cells.
- A potential signaling link between RET and FAK exists in non-MTC cell types.
Purpose of the Study:
- To investigate the hypothesis that RET inhibition decreases FAK phosphorylation in MTC cells.
- To implicate a RET-FAK signaling pathway in MTC.
Main Methods:
- Human MTC (TT) cells were treated with RET inhibitors or RET siRNA.
- Immunoblotting was used to detect total protein.
- FAK immunoprecipitation followed by antiphosphotyrosine immunoblotting detected phosphorylated FAK.
Main Results:
- The RET inhibitor PP2 significantly reduced RET and FAK phosphorylation.
- Imatinib mesylate inhibited FAK phosphorylation at high concentrations.
- RET siRNA significantly decreased RET expression and FAK phosphorylation.
Conclusions:
- RET signaling influences FAK in MTC cells, indicating a potential therapeutic pathway.
- The precise nature of the RET-FAK interaction (direct or indirect) requires further elucidation.
- RET inhibitors like PP2 may hold promise for MTC treatment.
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