title: Crucial roles of RSK in cell motility by catalysing serine phosphorylation of EphA2.
abstract: Crosstalk between inflammatory signalling pathways and receptor tyrosine kinases has been revealed as an indicator of cancer malignant progression. In the present study, we focus on EphA2 receptor tyrosine kinase, which is overexpressed in many human cancers. It has been reported that ligand-independent phosphorylation of EphA2 at Ser-897 is induced by Akt. We show that inflammatory cytokines promote RSK-, not Akt-, dependent phosphorylation of EphA2 at Ser-897. In addition, the RSK-EphA2 signalling pathway controls cell migration and invasion of metastatic breast cancer cells. Moreover, Ser-897-phosphorylated EphA2 co-localizes with phosphorylated active form of RSK in various human tumour specimens, and this double positivity is related to poor survival in lung cancer patients, especially those with a smoking history. Taken together, these results indicate that the phosphorylation of EphA2 at Ser-897 is controlled by RSK and the RSK-EphA2 axis might contribute to cell motility and promote tumour malignant progression.
authors.affiliation: Department of Cancer Cell Biology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Cancer Cell Biology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamada
authors.affiliation: Department of Cancer Cell Biology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Diagnostic Pathology, Toyama University Hospital, Toyama 930-0194, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Hori
authors.affiliation: Division of Pathogenic Biochemistry, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Yokoyama
authors.affiliation: Division of Pathogenic Biochemistry, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hayakawa
authors.affiliation: Division of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa 920-8641, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Yano
authors.affiliation: Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Fukuoka
authors.affiliation: Division of Kampo Diagnostics, Institute of Natural Medicine, University of Toyama 930-0194, Toyama, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Koizumi
authors.affiliation: Division of Pathogenic Biochemistry, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Saiki
authors.affiliation: Department of Cancer Cell Biology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Sakurai
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism; D002384:Catalysis; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism; D008297:Male; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism; D036104:Receptor, EphA2 / Q000378:metabolism*; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000235:genetics* / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D012694:Serine; D036104:Receptor, EphA2; C069329:RPS6KA1 protein, human; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C069330:ribosomal protein S6 kinase, 90kDa, polypeptide 3