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Role of copper transporter 1 (CTR1) in glioblastoma progression
Thesis   Open access

Role of copper transporter 1 (CTR1) in glioblastoma progression

Jacob Parfianowicz
Master of Science (M.S.), Drexel University
Jun 2019
DOI:
https://doi.org/10.17918/h2gt-5992
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Abstract

Glioblastoma multiforme Oncology
Copper is an important trace element and an essential micronutrient for many biological reactions. While all cells require certain levels of copper for survival, elevated copper levels are found in some tumors and have been suggested to contribute to cancer progression. Reduction of serum copper levels by copper chelation therapy has been investigated in glioblastoma (GBM) patient clinical trials; however, results of these trials were inconclusive and did not significantly increase patient survival. Nonetheless, reduction of copper levels within the tumor tissue itself may still be beneficial in reducing tumorigenesis. Copper is imported into mammalian cells through the primary copper transporter CTR1, and previous studies have documented its overexpression in other cancers types. Here we provide evidence that CTR1 is also overexpressed in GBM. Through the use of several gene knockdown methods, we show that CTR1 reduction results in decreased GBM cell growth in vitro. We further show that the mechanism behind this growth inhibition is via apoptosis and/or cell cycle arrest. We also demonstrate that knockdown of CTR1 in GBM cells results in a decrease in the activity of copper-dependent protein kinases MEK1 and CK2, enzymes that drive a number of critical oncogenic signaling pathways in GBM. Overall, we provide preliminary evidence supporting the hypothesis that CTR1 is a viable therapeutic target for reducing intracellular copper levels in GBM cells that may lead to a decrease in cancer progression.

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