A cytoskeleton regulator AVIL drives tumorigenesis in glioblastoma.

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, Hui Li

Nature communications 2020 Jul 10

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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.

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, Hui Li. A cytoskeleton regulator AVIL drives tumorigenesis in glioblastoma. Nature communications. 2020 Jul 10;11(1):3457