Abstract：
:Alisertib (MLN8237, ALS), an Aurora kinase A (AURKA) inhibitor, exerts potent anti-tumor effects in the treatment of solid tumor and hematologic malignancies in preclinical and clinical studies. However, the fully spectrum of molecular targets of ALS and its anticancer effect in the treatment of chronic myeloid leukemia (CML) are not clear. This study aimed to examine the proteomic responses to ALS treatment and unveil the molecular interactome and possible mechanisms for its anticancer effect in K562 cells using stable-isotope labeling by amino acids in cell culture (SILAC) approach. The proteomic data identified that ALS treatment modulated the expression of 1541 protein molecules (570 up; 971 down). The pathway analysis showed that 299 signaling pathways and 459 cellular functional proteins directly responded to ALS treatment in K562 cells. These targeted molecules and signaling pathways were mainly involved in cell growth and proliferation, cell metabolism, and cell survival and death. Subsequently, the effects of ALS on cell cycle distribution, apoptosis, and autophagy were verified. The flow cytometric analysis showed that ALS significantly induced G2/M phase arrest and the Western blotting assays showed that ALS induced apoptosis via mitochondria-dependent pathway and promoted autophagy with the involvement of PI3K/Akt/mTOR, p38 MAPK, and AMPK signaling pathways in K562 cells. Collectively, this study provides a clue to quantitatively evaluate the proteomic responses to ALS and assists in globally identifying the potential molecular targets and elucidating the underlying mechanisms of ALS for CML treatment, which may help develop new efficacious and safe therapies for CML treatment.
journal_name
Am J Transl Resjournal_title
American journal of translational researchauthors
Shu LP,Zhou ZW,Zi D,He ZX,Zhou SFsubject
Has Abstractpub_date
2015-11-15 00:00:00pages
2442-61issue
11issn
1943-8141journal_volume
7pub_type
杂志文章abstract：:[This corrects the article on p. 1295 in vol. 10, PMID: 29887946.]. ...
journal_title：American journal of translational research
pub_type： 杂志文章,已发布勘误
doi：
更新日期：2018-07-15 00:00:00
abstract：:B-cell lymphoma/leukaemia 11A (BCL11A) is a modulator of foetal-to-adult globin switching and is involved in brain development and normal lymphopoiesis. The three-dimensional structure of BCL11A and its structural domains had not yet been completely determined; hence, this study aimed to elucidate the structural domai...
journal_title：American journal of translational research
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abstract：:Glioblastoma multiforme (GBM) is one of the most malignant and aggressive brain tumors with great amount of hyaluronan (HA) secretion and CD44 overexpression (HA receptor). CD44 has been suggested as a cancer stem cells (CSCs) marker. However, several clinical studies have indicated that CD44low glioma cell exhibit CS...
journal_title：American journal of translational research
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doi：
更新日期：2017-11-15 00:00:00
abstract：:Chronic kidney disease (CKD) results in various central nervous systems (CNS) disorders including cognitive dysfunction, depression, anxiety, movement disorders, seizures and encephalopathy. Uremic retention products, oxidative stress, inflammation and impaired blood-brain barrier have been implicated as the major med...
journal_title：American journal of translational research
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doi：
更新日期：2018-07-15 00:00:00
abstract：:Observational research suggests that exercise may reduce the risk of breast cancer and improve survival. One proposed mechanism for the protective effect of aerobic exercise related to cancer risk and outcomes, but has not been examined definitively, is the immune response to aerobic exercise. Two prevailing paradigms...
journal_title：American journal of translational research
pub_type： 杂志文章,评审
doi：
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journal_title：American journal of translational research
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journal_title：American journal of translational research
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journal_title：American journal of translational research
pub_type： 杂志文章
doi：
更新日期：2010-01-01 00:00:00
abstract：BACKGROUND:Ulcerative colitis (UC) is a chronic inflammatory intestinal disease, and its morbidity is rising worldwide. Previous study indicated that astragaloside II (AS II), a monomeric compound, was used to treat bowel disease. However, the effects of AS II on UC remains unclear. Thus, this study aimed to investigat...
journal_title：American journal of translational research
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journal_title：American journal of translational research
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journal_title：American journal of translational research
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更新日期：2019-05-15 00:00:00
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journal_title：American journal of translational research
pub_type： 杂志文章
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journal_title：American journal of translational research
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journal_title：American journal of translational research
pub_type： 杂志文章
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更新日期：2019-11-15 00:00:00
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journal_title：American journal of translational research
pub_type： 杂志文章
doi：
更新日期：2020-06-15 00:00:00
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journal_title：American journal of translational research
pub_type： 杂志文章
doi：
更新日期：2016-09-15 00:00:00
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journal_title：American journal of translational research
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doi：
更新日期：2020-03-15 00:00:00
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journal_title：American journal of translational research
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journal_title：American journal of translational research
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journal_title：American journal of translational research
pub_type： 杂志文章
doi：
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journal_title：American journal of translational research
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doi：
更新日期：2016-08-15 00:00:00
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journal_title：American journal of translational research
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更新日期：2020-08-15 00:00:00
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journal_title：American journal of translational research
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更新日期：2020-10-15 00:00:00
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journal_title：American journal of translational research
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更新日期：2019-09-15 00:00:00
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journal_title：American journal of translational research
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更新日期：2009-01-01 00:00:00
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更新日期：2017-11-15 00:00:00
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更新日期：2017-05-15 00:00:00
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更新日期：2017-09-15 00:00:00
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doi：
更新日期：2019-07-15 00:00:00
