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Inhibition of Aurora kinases induces apoptosis and autophagy via AURKB/p70S6K/RPL15 axis in human leukemia cells

He, Si-Jia, Shu, Li-Ping, Zhou, Zhi-Wei, Yang, Tianxin, Duan, Wei, Zhang, Xueji, He, Zhi-Xu and Zhou, Shu-Feng 2016, Inhibition of Aurora kinases induces apoptosis and autophagy via AURKB/p70S6K/RPL15 axis in human leukemia cells, Cancer letters, vol. 382, no. 2, pp. 215-230, doi: 10.1016/j.canlet.2016.08.016.

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Title Inhibition of Aurora kinases induces apoptosis and autophagy via AURKB/p70S6K/RPL15 axis in human leukemia cells
Author(s) He, Si-Jia
Shu, Li-Ping
Zhou, Zhi-Wei
Yang, Tianxin
Duan, Wei
Zhang, Xueji
He, Zhi-Xu
Zhou, Shu-Feng
Journal name Cancer letters
Volume number 382
Issue number 2
Start page 215
End page 230
Total pages 16
Publisher Elsevier
Place of publication Amsterdam, The Netherlands
Publication date 2016-11-28
ISSN 1872-7980
Keyword(s) AURKB/RPL15/p70S6K axis
Apoptosis
Aurora kinase
Autophagy
Danusertib
Leukemia
Science & Technology
Life Sciences & Biomedicine
Oncology
CHRONIC MYELOID-LEUKEMIA
ACUTE LYMPHOBLASTIC-LEUKEMIA
CANCER-CELLS
MESENCHYMAL TRANSITION
SIGNALING PATHWAY
CYCLE ARREST
LUNG-CANCER
PI3K/AKT/MTOR PATHWAY
PROSTATE-CANCER
GASTRIC-CANCER
Summary Leukemia is a common malignancy of blood cells with poor prognosis in many patients. Aurora kinases, a family of serine/threonine kinases, play a key role in regulating cell division and mitosis and are linked to tumorigenesis, metastasis, and poor prognosis in many human cancers including leukemia and lymphoma. Danusertib (Danu) is a pan-inhibitor of Aurora kinases with few data available in leukemia therapy. This study aimed to identify new molecular targets for Aurora kinase inhibition in human leukemia cells using quantitative proteomic analysis followed by verification experiments. There were at least 2932 proteins responding to Danu treatment, including AURKB, p70S6K, and RPL15, and 603 functional proteins and 245 canonical signaling pathways were involved in regulating cell proliferation, metabolism, apoptosis, and autophagy. The proteomic data suggested that Danu-regulated RPL15 signaling might contribute to the cancer cell killing effect. Our verification experiments confirmed that Danu negatively regulated AURKB/p70S6K/RPL15 axis with the involvement of PI3K/Akt/mTOR, AMPK, and p38 MAPK signaling pathways, leading to the induction of apoptosis and autophagy in human leukemia cells. Further studies are warranted to verify the feasibility via targeting AURKB/p70S6K/RPL15 axis for leukemia therapy.
Language eng
DOI 10.1016/j.canlet.2016.08.016
Field of Research 111201 Cancer Cell Biology
1112 Oncology And Carcinogenesis
Socio Economic Objective 920102 Cancer and Related Disorders
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2016, Elsevier Ireland Ltd.
Persistent URL http://hdl.handle.net/10536/DRO/DU:30086869

Document type: Journal Article
Collection: School of Medicine
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