Related Experiment Video
Updated: Oct 1, 2025
Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy
Published on: October 4, 2019
Nucleolar localization of the ErbB3 receptor as a new target in glioblastoma
Marzia Tagliaferro1, Paolo Rosa1, Gian Carlo Bellenchi2,3,4
1Department of Medical-Surgical Sciences and Biotechnologies, University of Rome La Sapienza, Corso della Repubblica 79, 04100, Latina, Italy.
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.
Insights
Glioblastoma cells utilize the ErbB3 receptor in the nucleolus for ribosome synthesis and proliferation. Targeting nucleolar ErbB3 may offer a new therapeutic strategy for this aggressive brain tumor.
Area of Science:
- Cell Biology
- Cancer Research
- Molecular Oncology
Background:
- The nucleolus is vital for ribosome biogenesis and cell homeostasis.
- Cancer cells exhibit increased nucleolar metabolism due to oncogenic factors.
- Epidermal Growth Factor Receptor (EGFR) family members are found in cancer cell nuclei and nucleoli, but their roles are unknown.
Purpose of the Study:
- To investigate the nucleolar function of the ErbB3 receptor in glioblastoma.
- To explore the non-canonical role of ErbB3 in ribosome biogenesis and cell proliferation.
Main Methods:
- Studied ErbB3 relocalization in response to Neuregulin 1.
- Assessed pre-ribosomal RNA (pre-rRNA) synthesis.
- Investigated the effects of ErbB3 silencing and nucleolar stress on cell proliferation and cell cycle progression.
Main Results:
- Neuregulin 1 stimulation caused ErbB3 to move from the nucleolus to the cytoplasm, increasing pre-rRNA synthesis.
- ErbB3 silencing or inducing nucleolar stress reduced glioblastoma cell proliferation.
- Cell cycle progression was altered by ErbB3 manipulation and nucleolar stress.
Conclusions:
- Glioblastoma cells employ an ErbB3-mediated non-canonical pathway to regulate ribosome synthesis and proliferation.
- The nucleolar ErbB3 receptor presents a potential novel therapeutic target for glioblastoma treatment.
More Related Videos
Related Concept Videos
02:55The Nucleolus
02:38Mitogens and the Cell Cycle
02:22Regulated mRNA Transport
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
01:46Nuclear Localization Signals and Import