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A cytoskeleton regulator AVIL drives tumorigenesis in glioblastoma.
Nat Commun. 2020 Jul 10; 11(1):3457.NC

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.

Authors+Show Affiliations

Department of Pathology, School of Medicine, University of Virginia, Charlottesville, VA, 22908, USA.Department of Biochemistry and Molecular Genetics, School of Medicine, University of Virginia, Charlottesville, VA, 22908, USA.Department of Microbiology, Immunology, and Cancer Biology, School of Medicine, University of Virginia, Charlottesville, VA, 22908, USA.Tumor Hospital, Guangxi Medical University, Nanning, 530021, China.Department of Pathology, School of Medicine, University of Virginia, Charlottesville, VA, 22908, USA.Department of Pathology, School of Medicine, University of Virginia, Charlottesville, VA, 22908, USA.Department of Pathology, School of Medicine, University of Virginia, Charlottesville, VA, 22908, USA.Department of Biology, James Madison University, Harrisonburg, VA, 22807, USA.Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, 410011, China.Department of Pathology, School of Medicine, University of Virginia, Charlottesville, VA, 22908, USA.Department of Biology, University of Virginia, Charlottesville, VA, 22908, USA.Department of Pathology, School of Medicine, University of Virginia, Charlottesville, VA, 22908, USA.Department of Microbiology, Immunology, and Cancer Biology, School of Medicine, University of Virginia, Charlottesville, VA, 22908, USA.Department of Pathology, School of Medicine, University of Virginia, Charlottesville, VA, 22908, USA. hl9r@virginia.edu. Department of Biochemistry and Molecular Genetics, School of Medicine, University of Virginia, Charlottesville, VA, 22908, USA. hl9r@virginia.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32651364

Citation

Xie, Zhongqiu, et al. "A Cytoskeleton Regulator AVIL Drives Tumorigenesis in Glioblastoma." Nature Communications, vol. 11, no. 1, 2020, p. 3457.
Xie Z, Janczyk PŁ, Zhang Y, et al. A cytoskeleton regulator AVIL drives tumorigenesis in glioblastoma. Nat Commun. 2020;11(1):3457.
Xie, Z., Janczyk, P. Ł., Zhang, Y., Liu, A., Shi, X., Singh, S., Facemire, L., Kubow, K., Li, Z., Jia, Y., Schafer, D., Mandell, J. W., Abounader, R., & Li, H. (2020). A cytoskeleton regulator AVIL drives tumorigenesis in glioblastoma. Nature Communications, 11(1), 3457. https://doi.org/10.1038/s41467-020-17279-1
Xie Z, et al. A Cytoskeleton Regulator AVIL Drives Tumorigenesis in Glioblastoma. Nat Commun. 2020 Jul 10;11(1):3457. PubMed PMID: 32651364.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A cytoskeleton regulator AVIL drives tumorigenesis in glioblastoma. AU - Xie,Zhongqiu, AU - Janczyk,Pawel Ł, AU - Zhang,Ying, AU - Liu,Aiqun, AU - Shi,Xinrui, AU - Singh,Sandeep, AU - Facemire,Loryn, AU - Kubow,Kristopher, AU - Li,Zi, AU - Jia,Yuemeng, AU - Schafer,Dorothy, AU - Mandell,James W, AU - Abounader,Roger, AU - Li,Hui, Y1 - 2020/07/10/ PY - 2019/05/20/received PY - 2020/06/18/accepted PY - 2020/7/12/entrez PY - 2020/7/12/pubmed PY - 2020/7/12/medline SP - 3457 EP - 3457 JF - Nature communications JO - Nat Commun VL - 11 IS - 1 N2 - 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. SN - 2041-1723 UR - https://www.unboundmedicine.com/medline/citation/32651364/A_cytoskeleton_regulator_AVIL_drives_tumorigenesis_in_glioblastoma L2 - http://dx.doi.org/10.1038/s41467-020-17279-1 DB - PRIME DP - Unbound Medicine ER -
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