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Sumoylation of EphB1 Suppresses Neuroblastoma Tumorigenesis via Inhibiting PKCγ Activation

Qin Chen1,2, Rong Deng1, Xian Zhao1

  • 1Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
|March 19, 2018
PubMed
Abstract

Insights

Small ubiquitin-like modifier (SUMO)ylation of erythropoietin-producing hepatocellular carcinoma (Eph)B1 suppresses tumor growth by inhibiting PKCγ activation. SUMO1 is a novel regulator of EphB1-mediated tumorigenesis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Erythropoietin-producing hepatocellular carcinoma (Eph) family receptor tyrosine kinases are implicated in cancer progression.
  • Regulation of Eph family receptor tyrosine kinase function in cancer remains poorly understood.

Purpose of the Study:

  • To investigate the role of small ubiquitin-like modifier (SUMO)ylation in regulating EphB1 function in cancer.
  • To elucidate the mechanism by which SUMOylation affects EphB1-mediated tumorigenesis.

Main Methods:

  • SUMOylation was assessed using Ni2+-NTA pull-down and immunoprecipitation assays.
  • Cell proliferation, anchorage-independent growth, and in vivo tumorigenesis were evaluated using cell counting kit-8, soft agar assays, and xenograft mouse models, respectively.

Main Results:

  • EphB1 undergoes SUMOylation at lysine residue 785.
  • SUMOylation of EphB1 suppressed cell proliferation, anchorage-independent growth, and xenograft tumor growth.
  • SUMOylation of EphB1 repressed PKCγ activation, inhibiting tumorigenesis and establishing a reciprocal regulatory loop.

Conclusions:

  • SUMO1 acts as a novel key regulator of EphB1-mediated tumorigenesis.
  • SUMOylation of EphB1 is a critical mechanism for controlling its oncogenic activity.
Keywords:
EphB1NeuroblastomaPKCγSUMOylationTumorigenesis

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