Background/aims: An increasing number of studies have linked <unterline>e</unterline>rythropoietin-<unterline>p</unterline>roducing <unterline>h</unterline>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 Ni2+-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.
Keywords: EphB1; Neuroblastoma; PKCγ; SUMOylation; Tumorigenesis.
© 2018 The Author(s). Published by S. Karger AG, Basel.