title: Erk1/2 activation and modulation of STAT3 signaling in oral cancer.
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.
authors.affiliation: Department of Oral Pathology and Surgery, Dental School, National and Kapodistrian University of Athens, Athens 11527, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Gkouveris
authors.affiliation: Department of Oral Pathology and Surgery, Dental School, National and Kapodistrian University of Athens, Athens 11527, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Nikitakis
authors.affiliation: First Department of Pathology, Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Karanikou
authors.affiliation: First Department of Pathology, Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Rassidakis
authors.affiliation: Department of Oral Pathology and Surgery, Dental School, National and Kapodistrian University of Athens, Athens 11527, Greece.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Sklavounou
mesh_terms: D002070:Butadienes / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019938:Cyclin D1 / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D009062:Mouth Neoplasms / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D034741:RNA, Small Interfering / Q000494:pharmacology*; D050796:STAT3 Transcription Factor / Q000378:metabolism*
chemical_list: D002070:Butadienes; C530104:CCND1 protein, human; D009570:Nitriles; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C113580:U 0126; D019938:Cyclin D1