Thesis
Role of Spastin in regulating glioblastoma cell survival
Master of Science (M.S.), Drexel University
2017
DOI:
https://doi.org/10.17918/etd-7749
Abstract
Glioblastomas are the most aggressive form of brain tumors and the most abundant malignant glioma among adults. These are notoriously aggressive cancers with the median survival of 14.6 months after diagnosis. Thus, different strategies and targeted therapies are needed in order to improve prognosis and survival. Microtubules are an essential machinery to ensure proper cell division and proliferation. Uncontrolled cell division is the primary hallmark of cancer cells hence microtubule-targeting drugs are widely used in cancer therapeutics. However, resistance to those drugs has been a major hurdle that has compromised their success. In that regard, different microtubule associated proteins that affect its dynamic nature are widely explored as targets for cancer therapeutics. Spastin is a microtubule severing ATPase that directly modulates the dynamics of microtubules and Spastin levels have been shown to be elevated in the glioblastomas. Our lab has recently shown that targeting Spastin in glioblastoma cells causes restriction in tumor growth in an orthotopic xenograft mouse model. Here, we show that inhibiting Spastin using two different shRNAs in glioblastoma cells: U87 and T98Gs, induces apoptosis with a reduction in the apoptotic marker cleaved-PARP and downregulates the anti-apoptotic protein Bcl-2. Consistently, we noticed that Spastin depletion using shRNAs reduced cell attachment. Indeed, we show that the adhesion- dependent signaling pathways, Erk and p38 are reduced upon Spastin depletion in glioblastoma cells. Thus, Spastin maintains glioblastoma cell survival and tumorigenicity by maintaining the pro-survival signaling pathways in the cancer cells and may represent a novel therapeutic target in glioblastoma.
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Details
- Title
- Role of Spastin in regulating glioblastoma cell survival
- Creators
- Dimpi Mukhopadhyay - DU
- Contributors
- Mauricio Reginato (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Master of Science (M.S.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- 32 pages
- Resource Type
- Thesis
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; College of Medicine; Drexel University
- Other Identifier
- 7749; 991014632849304721