Erk1/2 activation and modulation of STAT3 signaling in oral cancer.

Oncology reports (2014-09-02)
Ioannis Gkouveris, Nikolaos Nikitakis, Maria Karanikou, George Rassidakis, Alexandra Sklavounou
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Hydrocortisone, BioReagent, suitable for cell culture
Sigma-Aldrich
Hydrocortisone, ≥98% (HPLC)
Sigma-Aldrich
Hydrocortisone, γ-irradiated, powder, BioXtra, suitable for cell culture
Supelco
Hydrocortisone, Pharmaceutical Secondary Standard; Certified Reference Material
USP
Hydrocortisone, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Hydrocortisone, meets USP testing specifications
Hydrocortisone for peak identification, European Pharmacopoeia (EP) Reference Standard
Hydrocortisone, European Pharmacopoeia (EP) Reference Standard
Supelco
Hydrocortisone, VETRANAL®, analytical standard
Hydrocortisone, British Pharmacopoeia (BP) Assay Standard