XRN2 Is Required for Cell Motility and Invasion in Glioblastomas
Tuyen T. Dang,
Megan Lerner,
Debra Saunders,
Nataliya Smith,
Rafal Gulej,
Michelle Zalles,
Rheal A. Towner,
Julio C. Morales
Affiliations
Tuyen T. Dang
Department of Neurosurgery, Sttephenson Cancer Center University of Oklahoma Health Science Center, Oklahoma City, OK 73104, USA
Megan Lerner
Department of Surgery, University of Oklahoma Health Science Center, Oklahoma City, OK 73104, USA
Debra Saunders
Department of Pathology, University of Oklahoma Health Science Center, Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA
Nataliya Smith
Department of Pathology, University of Oklahoma Health Science Center, Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA
Rafal Gulej
Department of Pathology, University of Oklahoma Health Science Center, Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA
Michelle Zalles
Department of Pathology, University of Oklahoma Health Science Center, Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA
Rheal A. Towner
Department of Pathology, University of Oklahoma Health Science Center, Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA
Julio C. Morales
Department of Neurosurgery, Sttephenson Cancer Center University of Oklahoma Health Science Center, Oklahoma City, OK 73104, USA
One of the major obstacles in treating brain cancers, particularly glioblastoma multiforme, is the occurrence of secondary tumor lesions that arise in areas of the brain and are inoperable while obtaining resistance to current therapeutic agents. Thus, gaining a better understanding of the cellular factors that regulate glioblastoma multiforme cellular movement is imperative. In our study, we demonstrate that the 5′-3′ exoribonuclease XRN2 is important to the invasive nature of glioblastoma. A loss of XRN2 decreases cellular speed, displacement, and movement through a matrix of established glioblastoma multiforme cell lines. Additionally, a loss of XRN2 abolishes tumor formation in orthotopic mouse xenograft implanted with G55 glioblastoma multiforme cells. One reason for these observations is that loss of XRN2 disrupts the expression profile of several cellular factors that are important for tumor invasion in glioblastoma multiforme cells. Importantly, XRN2 mRNA and protein levels are elevated in glioblastoma multiforme patient samples. Elevation in XRN2 mRNA also correlates with poor overall patient survival. These data demonstrate that XRN2 is an important cellular factor regulating one of the major obstacles in treating glioblastomas and is a potential molecular target that can greatly enhance patient survival.
