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Classical cadherins control survival through the gp130/Stat3 axis.
M Geletu1, R Arulanandam, S Chevalier
1Department of Microbiology and Immunology, Queen's University, Kingston, Ontario, Canada.
Biochimica Et Biophysica Acta
|April 2, 2013
Summary
Cadherin engagement, including E-cadherin, N-cadherin, and cadherin-11, activates Signal Transducer and Activator of Transcription-3 (Stat3), promoting cell survival and proliferation. This contrasts with Erk pathway activity, which is inhibited by cadherin engagement.
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- Signal Transducer and Activator of Transcription-3 (Stat3) is a key signaling molecule activated by various kinases.
- E-cadherin engagement was previously shown to activate Stat3.
- Classical cadherins play roles in cell adhesion and are implicated in cancer metastasis.
Purpose of the Study:
- To investigate the effect of cadherin-11 and N-cadherin engagement on Stat3 phosphorylation and activity.
- To explore the role of IL6 family cytokines in cadherin-mediated Stat3 activation.
- To examine the impact of cadherin engagement on Extracellular Signal Regulated kinase (Erk) activity.
Main Methods:
- Assessing Stat3 and Erk phosphorylation and activity upon engagement of cadherin-11 and N-cadherin.
- Analyzing the role of IL6 family cytokines in Stat3 activation.
- Utilizing cadherin-11 knock-down experiments to study Erk activation.
Main Results:
- Engagement of cadherin-11 and N-cadherin triggers a significant increase in Stat3 activity, mediated by IL6 family cytokines.
- Cadherin-11 engagement activates Stat3, which is essential for cell survival, proliferation, and migration.
- Unlike Stat3, Erk activity is unaffected by cadherin-11 engagement; cadherin engagement inhibits IL6-induced Erk activation in dense cultures.
Conclusions:
- Classical cadherins (E-cadherin, N-cadherin, cadherin-11) consistently activate Stat3, suggesting Stat3 acts as a central survival factor.
- Cadherin engagement plays a regulatory role in the Erk signaling pathway, distinct from its effect on Stat3.
- Stat3 activation by cadherins may be a fundamental mechanism for cell survival across various tissues, irrespective of metastatic potential.
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