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SLC7A11 Overexpression in Glioblastoma Is Associated with Increased Cancer Stem Cell-Like Properties

Polewski, Monika Dagmara and Reveron-Thornton, Rosyli Francis and Cherryholmes, Gregory Allan and Marinov, Georgi K. and Aboody, Karen Saida (2017) SLC7A11 Overexpression in Glioblastoma Is Associated with Increased Cancer Stem Cell-Like Properties. Stem Cells and Development, 26 (17). pp. 1236-1246. ISSN 1547-3287. PMCID PMC5576215.

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System x_c^− is a sodium-independent electroneutral transporter, comprising a catalytic subunit xCT (SLC7A11), which is involved in importing cystine. Certain cancers such as gliomas upregulate the expression of system x_c^−, which confers a survival advantage against the detrimental effects of reactive oxygen species (ROS) by increasing generation of the antioxidant glutathione. However, ROS have also been shown to function as targeted, intracellular second messengers in an array of physiological processes such as proliferation. Several studies have implicated ROS in important cancer features such as migration, invasion, and contribution to a cancer stem cell (CSC)-like phenotype. The role of system x_c^− in regulating these ROS-sensitive processes in glioblastoma multiforme (GBM), the most aggressive malignant primary brain tumor in adults, remains unknown. Stable SLC7A11 knockdown and overexpressing U251 glioma cells were generated and characterized to understand the role of redox and system x_c^− in glioma progression. SLC7A11 knockdown resulted in higher endogenous ROS levels and enhanced invasive properties. On the contrary, overexpression of SLC7A11 resulted in decreased endogenous ROS levels as well as decreased migration and invasion. However, SLC7A11-overexpressing cells displayed actin cytoskeleton changes reminiscent of epithelial-like cells and exhibited an increased CSC-like phenotype. The enhanced CSC-like phenotype may contribute to increased chemoresistance and suggests that overexpression of SLC7A11 in the context of GBM may contribute to tumor progression. These findings have important implications for cancer management where targeting system x_C^− in combination with other chemotherapeutics can reduce cancer resistance and recurrence and improve GBM patient survival.

Item Type:Article
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URLURL TypeDescription CentralArticle
Marinov, Georgi K.0000-0003-1822-7273
Alternate Title:SLC7A11 over-expression in glioblastoma is associated with increased cancer stem-cell like properties
Additional Information:© 2017 Mary Ann Liebert, Inc. Published in Volume: 26 Issue 17: September 1, 2017; Online Ahead of Print: July 27, 2017; Online Ahead of Editing: June 13, 2017. The authors acknowledge California Institute of Regenerative Medicine (TG2-01150), the Rosalinde and Arthur Gilbert Foundation, STOP Cancer, and the National Cancer Institute Cancer Center Support Grant (P30CA033572) for funding. The authors also acknowledge the technical support of the City of Hope RNAi Core (Dr. Claudia M. Kowolik), the Light Microscopy Digital Imaging Core (Dr. Brian Armstrong and Tina Patel), and Dr. Keely L. Walker for critical reading and editing of the article.
Funding AgencyGrant Number
California Institute of Regenerative MedicineTG2-01150
Rosalinde and Arthur Gilbert FoundationUNSPECIFIED
National Cancer InstituteUNSPECIFIED
Issue or Number:17
PubMed Central ID:PMC5576215
Record Number:CaltechAUTHORS:20170619-080855887
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Official Citation:Polewski Monika D., Reveron-Thornton Rosyli F., Cherryholmes Gregory A., Marinov Georgi K., and Aboody Karen S.. Stem Cells and Development. September 2017, 26(17): 1236-1246.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:78317
Deposited By: Tony Diaz
Deposited On:19 Jun 2017 16:15
Last Modified:30 Oct 2019 15:00

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