Knockdown of ephb1 receptor decreases medulloblastoma cell growth and migration and increases cellular radiosensitization

Shilpa Bhatia, Nimrah A. Baig, Olga Timofeeva, Elena B. Pasquale, Kellen Hirsch, Tobey J. MacDonald, Anatoly Dritschilo, Yi Chien Lee, Mark Henkemeyer, Brian Rood, Mira Jung, Xiao Jing Wang, Marcel Kool, Olga Rodriguez, Chris Albanese, Sana D. Karam

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

25 Citaten (Scopus)


The expression of members of the Eph family of receptor tyrosine kinases and their ephrin ligands is frequently dysregulated in medulloblastomas. We assessed the expression and functional role of EphB1 in medulloblastoma cell lines and engineered mouse models. mRNA and protein expression profiling showed expression of EphB1 receptor in the human medulloblastoma cell lines DAOY and UW228. EphB1 downregulation reduced cell growth and viability, decreased the expression of important cell cycle regulators, and increased the percentage of cells in G1 phase of the cell cycle. It also modulated the expression of proliferation, and cell survival markers. In addition, EphB1 knockdown in DAOY cells resulted in significant decrease in migration, which correlated with decreased β1-integrin expression and levels of phosphorylated Src. Furthermore, EphB1 knockdown enhanced cellular radiosensitization of medulloblastoma cells in culture and in a genetically engineered mouse medulloblastoma model. Using genetically engineered mouse models, we established that genetic loss of EphB1 resulted in a significant delay in tumor recurrence following irradiation compared to EphB1-expressing control tumors. Taken together, our findings establish that EphB1 plays a key role in medulloblastoma cell growth, viability, migration, and radiation sensitivity, making EphB1 a promising therapeutic target.

Originele taal-2Engels
Pagina's (van-tot)8929-8946
Aantal pagina's18
Nummer van het tijdschrift11
StatusGepubliceerd - 2015
Extern gepubliceerdJa


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