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Updated: Mar 12, 2026
Live-Cell Imaging Assays to Study Glioblastoma Brain Tumor Stem Cell Migration and Invasion
Published on: August 29, 2018
RSK2 activity mediates glioblastoma invasiveness and is a potential target for new therapeutics
Florian J Sulzmaier1, Shirley Young-Robbins1, Pengfei Jiang2
1Cancer Biology Program, University of Hawaii Cancer Center, University of Hawaii at Mānoa, Honolulu, HI 96813, USA.
Abstract:
In glioblastoma (GBM), infiltration of primary tumor cells into the normal tissue and dispersal throughout the brain is a central challenge to successful treatment that remains unmet. Indeed, patients respond poorly to the current therapies of tumor resection followed by chemotherapy with radiotherapy and have only a 16-month median survival. It is therefore imperative to develop novel therapies. RSK2 is a kinase that regulates proliferation and adhesion and can promote metastasis. We demonstrate that active RSK2 regulates GBM cell adhesion and is essential for cell motility and invasion of patient-derived GBM neurospheres. RSK2 control of adhesion and migration is mediated in part by its effects on integrin-Filamin A complexes. Importantly, inhibition of RSK2 by either RSK inhibitors or shRNA silencing impairs invasion and combining RSK2 inhibitors with temozolomide improves efficacy in vitro. In agreement with the in vitro data, using public datasets, we find that RSK2 is significantly upregulated in vivo in human GBM patient tumors, and that high RSK2 expression significantly correlates with advanced tumor stage and poor patient survival. Together, our data provide strong evidence that RSK inhibitors could enhance the effectiveness of existing GBM treatment, and support RSK2 targeting as a promising approach for novel GBM therapy.
Insights
Targeting RSK2 kinase in glioblastoma (GBM) inhibits tumor cell invasion and enhances chemotherapy efficacy. This approach offers a promising new strategy for treating aggressive brain tumors like GBM.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Cancer Metastasis
Background:
- Glioblastoma (GBM) presents a significant therapeutic challenge due to aggressive tumor cell infiltration and poor patient survival.
- Current treatments involving surgery, chemotherapy, and radiotherapy offer limited efficacy, highlighting the need for novel therapeutic strategies.
- RSK2 (Ribosomal S6 Kinase 2) is implicated in cell proliferation, adhesion, and metastasis, suggesting its potential role in GBM progression.
Purpose of the Study:
- To investigate the role of RSK2 in glioblastoma cell invasion and motility.
- To evaluate the therapeutic potential of inhibiting RSK2 in GBM treatment.
- To determine the correlation between RSK2 expression and patient outcomes in GBM.
Main Methods:
- Utilized patient-derived GBM neurospheres to assess RSK2 activity's impact on cell adhesion, motility, and invasion.
- Examined the molecular mechanisms involving RSK2, integrin, and Filamin A interactions.
- Tested the efficacy of RSK2 inhibitors, alone and in combination with temozolomide, in vitro.
- Analyzed public datasets to correlate RSK2 expression levels with GBM tumor stage and patient survival.
Main Results:
- Active RSK2 was found to be essential for GBM cell adhesion, motility, and invasion, partly through regulating integrin-Filamin A complexes.
- Inhibition of RSK2, using chemical inhibitors or shRNA, significantly impaired GBM cell invasion.
- Combining RSK2 inhibitors with temozolomide demonstrated improved therapeutic efficacy in vitro.
- RSK2 expression is significantly upregulated in human GBM tumors and correlates with advanced stage and poorer patient survival.
Conclusions:
- RSK2 plays a critical role in GBM cell invasion and motility.
- Targeting RSK2 presents a promising therapeutic strategy for glioblastoma.
- RSK2 inhibitors may enhance the effectiveness of current GBM treatments, including temozolomide.
