Nucleolar localization of the ErbB3 receptor as a new target in glioblastoma

BMC Molecular and Cell Biology

Francesco Fazi¹  Claudia Tito¹  Paolo Rosa²  Marzia Tagliaferro²  Antonella Calogero²  Donatella Ponti²  Gian Carlo Bellenchi³  Daniela Bastianelli⁴  Rosa Trotta⁵ 

[1] Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome;Department of Medical-Surgical Sciences and Biotechnologies, University of Rome La Sapienza;Institute of Genetics and Biophysics “Adriano Buzzati Traverso” CNR;Istituto Chirurgico Ortopedico Traumatologico;Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology (CCB), VIB;

关键词: ErbB3;    Neuregulin;    Nucleolus;    UBF;    Nucleolin;    Glioblastoma;   

DOI  :  10.1186/s12860-022-00411-y

来源: DOAJ

【 摘 要 】

Abstract Background The nucleolus is a subnuclear, non-membrane bound domain that is the hub of ribosome biogenesis and a critical regulator of cell homeostasis. Rapid growth and division of cells in tumors are correlated with intensive nucleolar metabolism as a response to oncogenic factors overexpression. Several members of the Epidermal Growth Factor Receptor (EGFR) family, have been identified in the nucleus and nucleolus of many cancer cells, but their function in these compartments remains unexplored. Results We focused our research on the nucleolar function that a specific member of EGFR family, the ErbB3 receptor, plays in glioblastoma, a tumor without effective therapies. Here, Neuregulin 1 mediated proliferative stimuli, promotes ErbB3 relocalization from the nucleolus to the cytoplasm and increases pre-rRNA synthesis. Instead ErbB3 silencing or nucleolar stress reduce cell proliferation and affect cell cycle progression. Conclusions These data point to the existence of an ErbB3-mediated non canonical pathway that glioblastoma cells use to control ribosomes synthesis and cell proliferation. These results highlight the potential role for the nucleolar ErbB3 receptor, as a new target in glioblastoma.

【 授权许可】

Unknown