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A cytoskeleton regulator AVIL drives tumorigenesis in glioblastoma

Author

Listed:
  • Zhongqiu Xie

    (University of Virginia)

  • Pawel Ł. Janczyk

    (University of Virginia)

  • Ying Zhang

    (University of Virginia)

  • Aiqun Liu

    (Guangxi Medical University)

  • Xinrui Shi

    (University of Virginia)

  • Sandeep Singh

    (University of Virginia)

  • Loryn Facemire

    (University of Virginia)

  • Kristopher Kubow

    (James Madison University)

  • Zi Li

    (Central South University)

  • Yuemeng Jia

    (University of Virginia)

  • Dorothy Schafer

    (University of Virginia)

  • James W. Mandell

    (University of Virginia)

  • Roger Abounader

    (University of Virginia)

  • Hui Li

    (University of Virginia
    University of Virginia)

Abstract

Glioblastoma is a deadly cancer, with no effective therapies. Better understanding and identification of selective targets are urgently needed. We found that advillin (AVIL) is overexpressed in all the glioblastomas we tested including glioblastoma stem/initiating cells, but hardly detectable in non-neoplastic astrocytes, neural stem cells or normal brain. Glioma patients with increased AVIL expression have a worse prognosis. Silencing AVIL nearly eradicated glioblastoma cells in culture, and dramatically inhibited in vivo xenografts in mice, but had no effect on normal control cells. Conversely, overexpressing AVIL promoted cell proliferation and migration, enabled fibroblasts to escape contact inhibition, and transformed immortalized astrocytes, supporting AVIL being a bona fide oncogene. We provide evidence that the tumorigenic effect of AVIL is partly mediated by FOXM1, which regulates LIN28B, whose expression also correlates with clinical prognosis. AVIL regulates the cytoskeleton through modulating F-actin, while mutants disrupting F-actin binding are defective in its tumorigenic capabilities.

Suggested Citation

  • Zhongqiu Xie & Pawel Ł. Janczyk & Ying Zhang & Aiqun Liu & Xinrui Shi & Sandeep Singh & Loryn Facemire & Kristopher Kubow & Zi Li & Yuemeng Jia & Dorothy Schafer & James W. Mandell & Roger Abounader &, 2020. "A cytoskeleton regulator AVIL drives tumorigenesis in glioblastoma," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17279-1
    DOI: 10.1038/s41467-020-17279-1
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