Abstract
The failure of existing therapies in treating human glioblastoma (GBM) mostly is due to the ability of GBM to infiltrate into healthy regions of the brain; however, the relationship between cell motility and cell mechanics is not well understood. Here, we used atomic force microscopy (AFM), live-cell imaging, and biochemical tools to study the connection between motility and mechanics in human GBM cells. It was found thatRac1 inactivation by genomic silencing and inhibition with EHT 1864 reduced cell motility, inhibited cell ruffles, and disrupted the dynamics of cytoskeleton organization and cell adhesion. These changes were correlated with abnormal localization of myosin IIa and a rapid suppression of the phosphorylation of Erk1/2. At the same time, AFM measurements of the GBM cells revealed a significant increase in cell elasticity and viscosity following Rac1 inhibition. These results indicate that mechanical properties profoundly affect cell motility and may play an important role in the infiltration of GBM. It is conceivable that the mechanical characters might be used as markers for further surgical and therapeutical interventions.
Highlights
Glioblastoma (GBM; World Health Organization grade IV glioma) is the most common and incurable primary brain tumor
Rac1 is the Rho GTPase family member that is mostly expressed in gliomas, and its level of expression correlates with patient survival outcome (Figure S1a,b)
To investigate whether Rac1 is required for GBM cell invasion, small interfering RNA against Rac1 was used to knockdown its expression in U87, U251, and T98G cells (Figure 1a and Figure S1c)
Summary
Glioblastoma (GBM; World Health Organization grade IV glioma) is the most common and incurable primary brain tumor. Its infiltration ability is largely responsible for the failure of existing therapies. Despite significant progress in developing targeted agents and immunotherapies, the prognosis of patients with GBM has not been improved markedly. Current GBM treatments focus on neurosurgical resection followed by radiation and chemotherapy. The median survival time of patients with GBM is less than fifteen months [1,2]. Novel diagnostic strategies and tools to rapidly determine the response of individual GBM to drugs are highly desirable to improve patient survival
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
