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Published on: June 15, 2016
Erk1/2 activation and modulation of STAT3 signaling in oral cancer
Ioannis Gkouveris1, Nikolaos Nikitakis1, Maria Karanikou2
1Department of Oral Pathology and Surgery, Dental School, National and Kapodistrian University of Athens, Athens 11527, Greece.
Abstract:
Constitutive activation of the signal transducer and activator of transcription 3 (STAT3) signaling pathway possesses confirmed oncogenic potential in oral squamous cell carcinoma (OSCC). Crosstalk with other molecular pathways contributes to STAT3 regulation in cancer. The effects of mitogen-activated protein kinases (MAPKs) and particularly extracellular signal-regulated kinase 1/2 (Erk1/2) on STAT3 signaling in OSCC have not been thoroughly investigated. The present study examined the effects of Erk1/2 modulation on STAT3 signaling and cell growth in OSCC cells. Constitutive expression levels of phosphorylated (tyrosine and serine) and total STAT3, Erk1/2 and cyclin D1 were assessed in OSCC cell lines. Erk1/2 modulation was achieved by pharmacological agents; siRNA silencing against Erk1/2 was also performed. Cell proliferation and viability were assessed. Erk1/2 inhibition with either U0126 treatment or specific siRNA silencing resulted in decreases in p-ser STAT3 and cyclin D1 levels and increases in p-tyr STAT3 in OSCC cells. Moreover, Erk1/2 inhibition resulted in a dose-dependent reduction in OSCC cell growth and viability. Erk1/2 induction had the opposite effects. Taken together, these results are supportive of an active crosstalk between the oncogenic Erk1/2 and STAT3 pathways in OSCC, the significance of which requires further investigation.
Insights
The extracellular signal-regulated kinase 1/2 (Erk1/2) pathway interacts with signal transducer and activator of transcription 3 (STAT3) in oral squamous cell carcinoma (OSCC). Inhibiting Erk1/2 reduces OSCC cell growth and viability.
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- Constitutive activation of the signal transducer and activator of transcription 3 (STAT3) pathway is oncogenic in oral squamous cell carcinoma (OSCC).
- The interplay between mitogen-activated protein kinases (MAPKs), specifically extracellular signal-regulated kinase 1/2 (Erk1/2), and STAT3 in OSCC remains underexplored.
Purpose of the Study:
- To investigate the impact of Erk1/2 modulation on STAT3 signaling and cellular growth in OSCC.
- To elucidate the crosstalk between Erk1/2 and STAT3 pathways in the context of oral cancer.
Main Methods:
- Assessed constitutive expression of phosphorylated (tyrosine and serine) and total STAT3, Erk1/2, and cyclin D1 in OSCC cell lines.
- Modulated Erk1/2 activity using pharmacological inhibitors (U0126) and siRNA silencing.
- Evaluated effects on cell proliferation and viability.
Main Results:
- Erk1/2 inhibition led to decreased p-ser STAT3 and cyclin D1 levels, alongside increased p-tyr STAT3 in OSCC cells.
- Pharmacological or genetic inhibition of Erk1/2 resulted in a dose-dependent reduction in OSCC cell growth and viability.
- Erk1/2 induction produced opposite effects on STAT3 signaling and cell growth.
Conclusions:
- Evidence suggests active crosstalk between the oncogenic Erk1/2 and STAT3 pathways in OSCC.
- This Erk1/2-STAT3 interaction plays a significant role in oral squamous cell carcinoma progression, warranting further investigation.
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