2. Academic Validation
  3. Crucial roles of RSK in cell motility by catalysing serine phosphorylation of EphA2

Crucial roles of RSK in cell motility by catalysing serine phosphorylation of EphA2

  • Nat Commun. 2015 Jul 9;6:7679. doi: 10.1038/ncomms8679.
Yue Zhou 1,  Naoki Yamada 1,  Tomohiro Tanaka 1,  Takashi Hori 2,  Satoru Yokoyama 3,  Yoshihiro Hayakawa 3,  Seiji Yano 4,  Junya Fukuoka 5,  Keiichi Koizumi 6,  Ikuo Saiki 3,  Hiroaki Sakurai 1
Affiliations

Affiliations

  • 1 Department of Cancer Cell Biology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan.
  • 2 Department of Diagnostic Pathology, Toyama University Hospital, Toyama 930-0194, Japan.
  • 3 Division of Pathogenic Biochemistry, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, Japan.
  • 4 Division of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa 920-8641, Japan.
  • 5 Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan.
  • 6 Division of Kampo Diagnostics, Institute of Natural Medicine, University of Toyama 930-0194, Toyama, Japan.
PMID: 26158630 DOI: 10.1038/ncomms8679
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.

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