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57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN)

German Society for Neuropathology and Neuroanatomy

12. - 15.09.2012, Erlangen

57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN)

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ZEB1 mediates invasion and chemoresistance of glioblastoma

Meeting Abstract

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  • presenting/speaker Florian Siebzehnrubl - Univ Florida McKnight Brain Institute, Neurosurgery, Gainesville, FL, United States
  • Daniel Silver - Univ Florida McKnight Brain Institute, Neurosurgery, Gainesville, FL, United States
  • Bugra Tugertimur - Univ Florida McKnight Brain Institute, Neurosurgery, Gainesville, FL, United States
  • Loic Deleyrolle - Univ Florida McKnight Brain Institute, Neurosurgery, Gainesville, FL, United States
  • Oleg Suslov - Univ Florida McKnight Brain Institute, Neurosurgery, Gainesville, FL, United States
  • Dorit Siebzehnrubl - Univ Florida McKnight Brain Institute, Neuroscience, Gainesville, FL, United States
  • Matthew Sarkisian - Univ Florida McKnight Brain Institute, Neuroscience, Gainesville, FL, United States
  • Kelly Devers - Univ Florida Shands Hospital, Pathology, Gainesville, FL, United States
  • Anthony Yachnis - Univ Florida Shands Hospital, Pathology, Gainesville, FL, United States
  • Marius Kuepper - Univ Bonn, Bonn, Germany
  • Nancy Nabilsi - Univ Florida Shands Cancer Center, Biochemistry and Molecular Biology, Gainesville, FL, United States
  • Michael Kladde - Univ Florida Shands Cancer Center, Biochemistry and Molecular Biology, Gainesville, FL, United States
  • Simone Brabletz - Univ Hospital Freiburg, Visceral Surgery, Freiburg, Germany
  • Thomas Brabletz - Univ Hospital Freiburg, Visceral Surgery, Freiburg, Germany
  • Brent Reynolds - Univ Florida McKnight Brain Institute, Neurosurgery, Gainesville, FL, United States
  • Dennis Steindler - Univ Florida McKnight Brain Institute, Neurosurgery, Gainesville, FL, United States

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie. 57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN). Erlangen, 12.-15.09.2012. Düsseldorf: German Medical Science GMS Publishing House; 2012. Doc12dgnnPP3.6

doi: 10.3205/12dgnn050, urn:nbn:de:0183-12dgnn0501

Published: September 11, 2012

© 2012 Siebzehnrubl et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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Despite intense efforts in basic research and clinical medicine, glioblastoma remains one of the most lethal types of cancer. In particular, tumor recurrence after surgical resection, aggressive chemotherapy, and targeted radiation remains an insurmountable obstacle. Recurrence has been attributed to residual cancer cells that re-initiate tumor growth after primary clinical intervention. Here, we provide new evidence that a subpopulation of invasive and chemoresistant cancer cells is maintained by the transcription factor ZEB1 (zinc finger E-box binding homeobox 1). ZEB1 is preferentially expressed in invasive glioblastoma cells, and its knockdown results in a dramatic reduction of tumor invasion as well as increased sensitivity to the chemotherapeutic agent Temozolomide (Temodar®, TMZ) in vitro and in vivo. By regulating both cell-cell adhesion, as well as expression of the chemoresistance-mediating enzyme MGMT (O-6-Methylguanine DNA Methyltransferase), this activator of epithelial-mesenchymal transition (EMT) links chemoresistance directly to brain tumor invasion. We further identify a novel pathway for the regulation of chemoresistance in glioma. Importantly, ZEB1 expression in glioblastoma patients correlates with tumor grade and is predictive of shorter survival and failure of chemotherapy. These results indicate that ZEB1 activation promotes invasion and protects glioblastoma cells from current therapeutic approaches. We thus identify ZEB1 as an important candidate molecule for glioblastoma recurrence, a potential marker of invasive tumor cells and a promising therapeutic target.