Open AccessSumoylation of EphB1 Suppresses Neuroblastoma Tumorigenesis via Inhibiting PKCγ Activation
Author(s) -
Chen Qin,
Deng Rong,
Zhao Xian,
Yuan Haihua,
Zhang Hailong,
Dou Jinzhuo,
Chen Ran,
Jin Hui,
Wang Yanli,
Huang Jian,
Yu Jianxiu
Publication year - 2018
Publication title -
cellular physiology and biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.486
H-Index - 87
eISSN - 1421-9778
pISSN - 1015-8987
DOI - 10.1159/000488174
Subject(s) - original paper
Background/Aims: An increasing number of studies have linked e rythropoietin- p roducing h epatocellular carcinoma (Eph) family receptor tyrosine kinases to cancer progression. However, little knowledge is available about the regulation of their functions in cancer. Methods: SUMOylation was analyzed by performing Ni 2+ -NTA pull-down assay and immunoprecipitation. Cell proliferation, anchorage-independent growth, and tumorigenesis in vivo were examined by cell counting kit-8, soft agar colony formation assay, and a xenograft tumor mouse model, respectively. Results: We found that EphB1 was post-translationally modified by the small ubiquitin-like modifier (SUMO) protein at lysine residue 785. Analysis of wild-type EphB1 and SUMOylation-deficient EphB1 K785R mutant revealed that SUMOylation of EphB1 suppressed cell proliferation, anchorage-independent cell growth, and xenograft tumor growth. Mechanistic study showed that SUMOylation of EphB1 repressed activation of its downstream signaling molecule PKCγ, and consequently inhibited tumorigenesis. A reciprocal regulatory loop between PKCγ and SUMOylation of EphB1 was also characterized. Conclusion: Our findings identify SUMO1 as a novel key regulator of EphB1-mediated tumorigenesis.