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LATS2 Inhibits Malignant Behaviors of Glioma Cells via Inactivating YAP

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Abstract

We previously reported that LATS2, the upstream serine/threonine kinase of Yes-associated protein (YAP), is downregulated in gliomas and exhibits negative correlation with the prognosis of glioma patients. In this work, we aimed to explore the role and mechanism of large tumor suppressor kinase (LATS2) in the progression of malignant gliomas. We found that over-expression of LATS2 inhibited glioma cell proliferation and migration/invasion, while LATS2 downregulation promoted them. Mechanistically, LATS2 promoted the phosphorylation of YAP without affecting YAP mRNA expression. Inconsistent with some previous reports, both YAPWT and YAP5SA did not affect the level of LATS2, suggesting that LATS2 did not form a feedback loop with YAP in gliomas. Furthermore, mammalian Ste20-like kinases (MST1) over-expression did not affect the phosphorylation of YAP, suggesting that MST1 may not be the essential upstream serine/threonine kinase of Hippo/YAP pathway in gliomas. Together, LATS2 inhibits glioma cell proliferation and migration/invasion by inactivating YAP.

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Funding

This study was funded by National Natural Science Foundation of China (No. 81672489; No. 81472345; No. 81872053).

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Author notes

  1. Yi Shi and Decheng Geng contributed equally to this work.

Authors and Affiliations

  1. Institute of Nervous System Diseases, Xuzhou Medical University, 84 West Huai-hai Road, Xuzhou, 221002, Jiangsu, People’s Republic of China

    Yi Shi, Decheng Geng, Yu Zhang, Min Zhao, Yan Wang, Yang Jiang, Rutong Yu & Xiuping Zhou

  2. Brain Hospital, Affiliated Hospital of Xuzhou Medical University, 99 West Huai-hai Road, Xuzhou, 221002, Jiangsu, People’s Republic of China

    Yi Shi, Decheng Geng, Yu Zhang, Min Zhao, Yan Wang, Yang Jiang, Rutong Yu & Xiuping Zhou

  3. The Graduate School, Xuzhou Medical University, Xuzhou, Jiangsu, China

    Yi Shi, Decheng Geng, Yu Zhang, Min Zhao & Yang Jiang

Authors
  1. Yi Shi
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  2. Decheng Geng
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  3. Yu Zhang
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  4. Min Zhao
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  7. Rutong Yu
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Corresponding authors

Correspondence to Rutong Yu or Xiuping Zhou.

Ethics declarations

Glioma tissues diagnosed according to the 2007 World Health Organization classification were collected from Brain Hospital, Affiliated Hospital of Xuzhou Medical University during year 2014–2015. There are 55 cases of glioma samples, including 22 cases of astrocytomas (grade II), 17 cases of anaplastic astrocytomas (grade III), and 16 cases of glioblastomas (grade IV). Eighteen nontumorous brain tissues were obtained from internal decompression of patients with cerebral injury. Written informed consent was obtained from each patient, and the study was approved by the ethics committee of the hospital.

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Shi, Y., Geng, D., Zhang, Y. et al. LATS2 Inhibits Malignant Behaviors of Glioma Cells via Inactivating YAP. J Mol Neurosci 68, 38–48 (2019). https://doi.org/10.1007/s12031-019-1262-z

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  • DOI: https://doi.org/10.1007/s12031-019-1262-z

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