Abstract:
BACKGROUND:Oncogenic roles of epidermal growth factor receptor pathway substrate no.8 (EPS8) have been widely reported in various tumors, making targeting of EPS8 an appealing prospect. Here, we describe the role of EPS8 in acute myeloid leukemia (AML) and consider the potential of EPS8 as an anti-AML target. Nuclear localization signal (NLS) residues of tumor-associated proteins are crucial for cell cycle progression, and specific inhibitors derived from the NLS have inhibitory effect on cancer cells. The NLS in EPS8 has potential as a specific anti-AML target. METHODS:Gene Expression Omnibus expression profiles of AML patients were used to test associations between EPS8 expression and AML patient outcome. The biological characteristics of AML cells after EPS8 knockdown were analyzed in vitro and in vivo. A specific peptide (CP-EPS8-NLS) derived from the NLS of EPS8 (amino acids 298-310) was synthesized, and the anti-AML effects of CP-EPS8-NLS were analyzed in cancer cells and in xenograft models. Mutated CP-EPS8-NLS and penetratin served as controls. RESULTS:We observed that elevated EPS8 expression in AML patients is associated with poor outcome. Knockdown of EPS8 significantly suppressed the survival of AML cells in vitro and in vivo. CP-EPS8-NLS interfered with EPS8-associated signaling and consequently exerted anti-AML activity. Importantly, CP-EPS8-NLS displayed anti-AML activity in various AML cell types, with diminished activity in PBMCs. CP-ESP8-NLS suppressed U937 cell proliferation, and injection of CP-EPS8-NLS exerted potent antitumor activity in the xenograft tumor models. A synergistic effect of CP-EPS8-NLS and chemotherapeutic agents was also observed in vitro and in vivo. Mechanistically, treatment of various AML cells with CP-EPS8-NLS downregulated the expression of EPS8 and its downstream pathways. CONCLUSIONS:The function of CP-EPS8-NLS is explained by the presence of a NLS in EPS8, which has been shown to induce nuclear translocation, consequently resulting in EPS8 overexpression. These results indicate that EPS8 is a potential target for AML treatment.
journal_name
J Exp Clin Cancer Resjournal_title
Journal of experimental & clinical cancer research : CRauthors
Chen Y,Xie X,Wu A,Wang L,Hu Y,Zhang H,Li Ydoi
10.1186/s13046-018-0682-xsubject
Has Abstractpub_date
2018-01-22 00:00:00pages
12issue
1eissn
0392-9078issn
1756-9966pii
10.1186/s13046-018-0682-xjournal_volume
37pub_type
杂志文章abstract:BACKGROUND:The aim of this study was to evaluate the potential association between single nucleotide polymorphisms related response to radiotherapy injury, such as genes related to DNA repair or enzymes involved in anti-oxidative activities. The paper aims to identify marker genes able to predict an increased risk of l...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 临床试验,杂志文章
doi:10.1186/1756-9966-31-7
更新日期:2012-01-24 00:00:00
abstract:BACKGROUND:Hippo/YAP pathway is known to be important for development, growth and organogenesis, and dysregulation of this pathway leads to tumor progression.We and others find that YAP is up-regulated in human gliomas and associated with worse prognosis of patients. However, the role and mechanism of YAP in glioma pro...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-017-0606-1
更新日期:2017-09-29 00:00:00
abstract:BACKGROUND:Ewing's sarcoma is an aggressive bone and soft tissue tumor with a high incidence in children and adolescents. Due to its high malignancy and poor prognosis, identification of novel biomarkers for intervention therapies is necessary to improve outcome. The EWS/FLI1 fusion gene is a characteristic of Ewing's ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-016-0321-3
更新日期:2016-03-11 00:00:00
abstract::This case report describes a rare presentation of penile melanoma in which 3 successive primaries arose and were operated from an area of melanosis on the glans penis and prepuce. One of the major factors accounting for the poor prognosis of this patient was the long delay in presentation. This was largely due to the ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:1999-06-01 00:00:00
abstract::Hepatocellular carcinoma (HCC) ranks the most common primary liver malignancy and the third leading cause of tumor-related mortality worldwide. Unfortunately, despite advances in HCC treatment, less than 40% of HCC patients are eligible for potentially curative therapies. Recently, cancer immunotherapy has emerged as ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,评审
doi:10.1186/s13046-019-1396-4
更新日期:2019-09-09 00:00:00
abstract::Cancer vaccine therapy represents a promising therapeutical option. Consistently, with these new treatment strategies, the use of dendritic cell vaccines is becoming increasingly widespread and currently in the forefront for cancer treatment. The purpose of this study was to evaluate the feasibility and safety of tumo...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2007-06-01 00:00:00
abstract::Glioblastoma multiform (GBM) is the most common tumour of the central nervous system in humans. Unfortunately its prognosis is poor and because of the lack of efficacious therapies, immunotherapy is a potential treatment. Transfer factors (TF) are low molecular weight dialysable products extracted from immune cells wh...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2005-12-01 00:00:00
abstract:BACKGROUND:Expression of the Sp1 transcription factor is induced by hypoxia, and the ADAM17 promoter contains predicted Sp1 binding sites. ADAM17 contributes to hypoxic-induce invasiveness of glioma. In this study, we investigated whether Sp1 transcription factor induces ADAM17 and/or contributes to tumor cell invasive...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-28-129
更新日期:2009-09-22 00:00:00
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journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,评审
doi:10.1186/s13046-019-1085-3
更新日期:2019-02-18 00:00:00
abstract::Gastric cancer, characterized by poor prognosis, remains a global health problem. Thus, it is important to describe the biological factors which can affect the prognosis in this disorder. The aim of our study was the determination of the relationship between apoptotic index (AI) and other clinicopathological features ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2002-09-01 00:00:00
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journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-016-0340-0
更新日期:2016-04-12 00:00:00
abstract:BACKGROUND:Breast cancer is the most common cancer among women worldwide, and approximately 70% of breast cancers are hormone receptor-positive and express estrogen receptor-α (ERα) or/and progesterone receptor. ERα has been identified to promote the growth of primary breast cancer, however, it can also antagonize sign...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-019-1112-4
更新日期:2019-03-01 00:00:00
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journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-32-61
更新日期:2013-09-02 00:00:00
abstract:BACKGROUND:The preferential use of aerobic glycolysis by tumor cells lead to high accumulation of lactate in tumor microenvironment. Clinical evidence has linked elevated lactate concentration with cancer outcomes. However, the role and molecular mechanisms of lactate in cellular senescence and tumor progression remain...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-018-0701-y
更新日期:2018-02-26 00:00:00
abstract:BACKGROUND:The histone methyltransferase G9a has recently been identified as a potential target for epigenetic therapy of acute myeloid leukemia (AML). However, the effect of G9a inhibition on leukemia stem cells (LSCs), which are responsible for AML drug resistance and recurrence, is unclear. In this study, we investi...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-020-01565-3
更新日期:2020-04-15 00:00:00
abstract:BACKGROUND:Androgen receptor (AR) is expressed in approximately 70% of breast tumors. Recent studies increasingly support AR as a potential therapeutic target of AR-positive breast cancer. We have previously reported that deubiquitinase USP14 stabilizes AR proteins by deubiquitination and USP14 inhibition results in in...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-019-1227-7
更新日期:2019-05-24 00:00:00
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journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-016-0397-9
更新日期:2016-08-11 00:00:00
abstract::Since the social and financial impact of AML therapy is becoming more and more relevant we analyzed the cost of induction therapy of two different regimens. The first one is part of the widely employed EORTC-GIMEMA AML-10 and consists often days of therapy. The second (FLANG) is a short (three day), Fludarabine, Ara-C...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2001-06-01 00:00:00
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journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-018-0764-9
更新日期:2018-04-27 00:00:00
abstract::Radiofrequency Thermal Ablation (RFA) of liver tumors is done by percutaneous, laparoscopic and open surgical approach. Selection criteria for percutaneous or open surgical ablation of 65 hepatic lesions are here evaluated in 45 patients treated in a two-years period. Twenty-five patients were males and 20 females, ag...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2003-12-01 00:00:00
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journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-30-23
更新日期:2011-02-23 00:00:00
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journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-28-49
更新日期:2009-04-09 00:00:00
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journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,评审
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更新日期:2011-05-17 00:00:00
abstract::Increased expression of sialyl Lewis antigens, sLe(a) and sLe(x), is frequent during malignant transformation and tumor progression of gastrointestinal cancers and it is assumed to be correlated with the increased metastatic potential of tumor cells and, consequently, with poor patient survival. To determine the influ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:1999-09-01 00:00:00
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journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:1999-09-01 00:00:00
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journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-28-147
更新日期:2009-12-03 00:00:00
abstract::Patients with ulcerative colitis (UC) have a higher incidence of colorectal cancer. UC-associated colorectal cancer is thought to develop in patients with preexisting UC-associated dysplasia. It is crucial to diagnose UC-associated dysplasia and early stage of cancer in patients with long-standing UC for the purpose o...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2003-03-01 00:00:00
abstract::The renal oncocytoma is a solid epithelial neoplasm with a generally benign course. The improved image diagnostics with the computerized tomography (CT) and magnetic resonance imaging (MRI) should today permit the identification of these lesions preoperatively so that conservative rather than radical surgery can be em...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2000-09-01 00:00:00
abstract:BACKGROUND:Melanomas are highly malignant and have high metastatic potential; hence, there is a need for new therapeutic strategies to prevent cell metastasis. In the present study, we investigated whether statins inhibit tumor cell migration, invasion, adhesion, and metastasis in the B16BL6 mouse melanoma cell line. ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-29-127
更新日期:2010-09-16 00:00:00
abstract:BACKGROUND:Viscum album L. extracts (VAE, European mistletoe) are a widely used medicinal plant extract in gynaecological and breast-cancer treatment. METHODS:Systematic review to evaluate clinical studies and preclinical research on the therapeutic effectiveness and biological effects of VAE on gynaecological and bre...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,评审
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更新日期:2009-06-11 00:00:00