Abstract:
BACKGROUND:The cisplatin-resistance is still a main course for chemotherapy failure of lung cancer patients. Cisplatin-resistant cancer cells own higher malignance and exhibited increased metastatic ability, but the mechanism is not clear. In this study, we investigated the effects of Ataxia Telangiectasia Mutated (ATM) on lung cancer metastasis. MATERIALS AND METHODS:Cisplatin-resistant A549CisR and H157CisR cell line were generated by long-term treating parental A549 and H157 cells (A549P and H157P) with cisplatin. Cell growth, cell migration and cell invasion were determined. Gene expressions were determined by Western Blot and qPCR. Tumor metastasis was investigated using a xenograft mouse model. RESULTS:The IC50 of the cisplatin-resistant cells (A549CisR and H157CisR cells) to cisplatin was 6-8 higher than parental cells. The A549CisR and H157CisR cells expressed lower level of E-cadherin and higher levels of N-cadherin, Vimentin and Snail compared to the parental A549P and H157P cells, and exhibited stronger capabilities of metastatic potential compared to the parental cells. The ATM expression was upregulated in A549CisR and H157CisR cells and cisplatin treatment also upregulated expression of ATM in parental cells, The inhibition of ATM by using specific ATM inhibitor CP466722 or knock-down ATM by siRNA suppressed Epithelial-to-Mesenchymal transition (EMT) and metastatic potential of A549CisR and H157CisR cells. These data suggest that ATM mediates the cisplatin-resistance in lung cancer cells. Expressions of JAK1,2,、 STAT3 、PD-L1 and ATM were increased in A549CisR and H157CisR cells and could by induced by cisplatin in parental lung cancer cells. Interestedly, ATM upregulated PD-L1 expression via JAK1,2/STAT3 pathway and inhibition of ATM decreased JAK/STAT3 signaling and decreased PD-L1 expression. The treatment of PD-L1 neutralizing Ab reduced EMT and cell invasion. Inhibition of JAK1,2/STAT3 signaling by specific inhibitors suppressed ATM-induced PD-L1 expression, EMT and cell invasion. Importantly, inhibition of ATM suppressed EMT and tumor metastasis in cisplatin-resistant lung cancer cells in an orthotopic xenograft mouse model. CONCLUSIONS:Our results show that ATM regulates PD-L1 expression through activation of JAK/STAT3 signaling in cisplatin-resistant cells. Overexpression of ATM contributes to cisplatin-resistance in lung cancer cells. Inhibition of ATM reversed EMT and inhibited cell invasion and tumor metastasis. Thus, ATM may be a potential target for the treatment of cisplatin-resistant lung cancer.
journal_name
J Exp Clin Cancer Resjournal_title
Journal of experimental & clinical cancer research : CRauthors
Shen M,Xu Z,Xu W,Jiang K,Zhang F,Ding Q,Xu Z,Chen Ydoi
10.1186/s13046-019-1161-8subject
Has Abstractpub_date
2019-04-08 00:00:00pages
149issue
1eissn
0392-9078issn
1756-9966pii
10.1186/s13046-019-1161-8journal_volume
38pub_type
杂志文章abstract:BACKGROUND:Cancer-associated fibroblasts (CAFs), the primary component of tumor stroma in tumor microenvironments, are well-known contributors to the malignant progression of gallbladder cancer (GBC). Thrombospondins (THBSs or TSPs) comprise a family of five adhesive glycoproteins that are overexpressed in many types o...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-020-01812-7
更新日期:2021-01-06 00:00:00
abstract:BACKGROUND:MicroRNAs (miRNAs) posttranscriptionally regulate gene expression and thereby contribute to the modulation of numerous complex and disease-relevant cellular processes, including cell proliferation, cell motility, apoptosis and stress response. miRNA-31-5p is encoded on a genomic fragile site, 9p21.3, which i...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,收录出版
doi:10.1186/s13046-018-0930-0
更新日期:2018-11-06 00:00:00
abstract:BACKGROUND:Ubiquitin-like protein 4A (UBL4A) plays a significant role in protein metabolism and the maintenance of cellular homeostasis. In cancer, UBL4A represses tumorigenesis and is involved in various signaling pathways. Pancreatic ductal adenocarcinoma (PDAC) is still a major cause of cancer-related death and the ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-019-1278-9
更新日期:2019-07-09 00:00:00
abstract:BACKGROUND:This study aimed to analyze three-dimensional (3D) dosimetric data of conventional two-dimensional (2D) palliative spinal bone irradiation using different reference points and treatment plans with respect to the International Commission on Radiation Units and Measurements (ICRU) Report 50. METHODS:Forty-fiv...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-28-2
更新日期:2009-01-07 00:00:00
abstract:BACKGROUND:Microtubule Targeting Agents (MTAs) including paclitaxel, colchicine and vinca alkaloids are widely used in the treatment of various cancers. As with most chemotherapeutic agents, adverse effects and drug resistance are commonly associated with the clinical use of these agents. Methyl 2-(5-fluoro-2-hydroxyph...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-016-0332-0
更新日期:2016-03-31 00:00:00
abstract:BACKGROUND:In spite of recent advances in diagnostic and therapeutic measures, the prognosis of hepatocellular carcinoma (HCC) patients remains poor. Therefore, it is crucial to understand what factors are involved in promoting development of HCC. Evidence is accumulating that members of the chemokine receptor family a...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-29-31
更新日期:2010-04-11 00:00:00
abstract::After aggressive surgery and chemotherapy, patients (PTS) with advanced solid tumors have often an impaired immune function that may facilitate tumor relapse. We have demonstrated, in a phase IB study, that administering low-dose interleukin-2 (IL-2) and 13-cis retinoic acid (RA), there was a significant improvement o...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 临床试验,杂志文章
doi:
更新日期:2003-12-01 00:00:00
abstract:BACKGROUND:Novel therapeutic strategies are urgently needed for the treatment of metastatic Urothelial Bladder Cancer. DNA damaging repair (DDR) targeting has been introduced in cinical trials for bladder cancer patients that carry alterations in homologous DNA repair genes, letting to envisage susceptibility to the Po...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,评审
doi:10.1186/s13046-019-1089-z
更新日期:2019-02-22 00:00:00
abstract:BACKGROUND:Pancreatic cancer is a lethal disease in part because of its potential for aggressive invasion and metastasis. Lipoxin A4 (LXA4) is one of the metabolites that is derived from arachidonic acid and that is catalyzed by 15-lipoxygenase (15-LOX), and it has recently been reported to exhibit anti-cancer effects....
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-017-0655-5
更新日期:2017-12-11 00:00:00
abstract::Two-year protocols are commonly used for long-term assay of chemicals for carcinogenicity. However, in some cases, if animals have been exposed to tested agent from the young age and sacrificed at the age of 2, an underestimation of the carcinogenic potential of non-genotoxic agents and tumor promoters is possible. Da...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,评审
doi:
更新日期:1998-09-01 00:00:00
abstract:BACKGROUND:Gastric cancer (GC) is one of the most common malignant tumors worldwide. Currently, the overall survival rate of GC is still unsatisfactory despite progress in diagnosis and treatment. Therefore, studying the molecular mechanisms involved in GC is vital for diagnosis and treatment. CircRNAs, a type of nonco...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-020-01791-9
更新日期:2021-01-05 00:00:00
abstract:BACKGROUND:Peroxiredoxins (Prxs) are a novel group of peroxidases containing high antioxidant efficiency. The mammalian Prx family has six distinct members (Prx I-VI) in various subcellular locations, including peroxisomes and mitochondria, places where oxidative stress is most evident. The function of Prx I in particu...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-28-93
更新日期:2009-06-30 00:00:00
abstract::An amendment to this paper has been published and can be accessed via the original article. ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,撤回出版物
doi:10.1186/s13046-020-01668-x
更新日期:2020-08-19 00:00:00
abstract:BACKGROUD:Accumulating evidences indicate that circular RNAs (circRNAs), a class of non-coding RNAs, play important roles in tumorigenesis. However, the function of circRNAs in triple negative breast cancer (TNBC) is largely unknown. METHODS:We performed circRNA microarrays to identify circRNAs that are aberrantly exp...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-017-0614-1
更新日期:2017-10-16 00:00:00
abstract::CML is characterized by a reciprocal translocation between the abl and bcr genes on chromosomes 9 and 22 and is usually diagnosed by the presence of the Philadelphia (Ph1) chromosome.However, the translocation may also occur without the appearance of the Ph1 chromosome. In this study the diagnostic efficiency of the m...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:1997-03-01 00:00:00
abstract:BACKGROUND:Next generation sequencing (NGS) is being increasingly applied for assisting cancer molecular diagnosis. However, it is still needed to validate NGS accuracy on detection of DNA alternations based on a large number of clinical samples, especially for DNA rearrangements and copy number variations (CNVs). This...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-017-0591-4
更新日期:2017-09-07 00:00:00
abstract::In the original publication of this article [1], the authors reported the order of the authors was incorrect and needs to be revised. The original article has been updated to rectify this error. ...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 已发布勘误
doi:10.1186/s13046-019-1338-1
更新日期:2019-08-02 00:00:00
abstract:BACKGROUND:Triple negative breast cancer (TNBC) is an aggressive neoplasia with no effective therapy. Our laboratory has developed a unique TNBC cell model presenting epithelial mesenchymal transition (EMT) a process known to be important for tumor progression and metastasis. There is increasing evidence showing that e...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-018-0988-8
更新日期:2018-12-14 00:00:00
abstract:BACKGROUND:In this research, we aimed to resolve contradictory results whether SOX9 plays a positive or negative role in melanoma progression and determine whether SOX9 and its closely related member SOX10 share the same or distinct targets in mediating their functions in melanoma. METHODS:Immunofluorescence, TCGA dat...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-018-0998-6
更新日期:2019-01-14 00:00:00
abstract::Myelodysplastic syndromes (MDS) are a heterogenous group of hematological clonal malignancies. Patients belonging to the refractory anemia (RA) subtype are usually treated with recombinant human erythropoietin (EPO). Not all patients respond to EPO administration and they are strictly dependent on supportive therapy w...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2004-03-01 00:00:00
abstract:BACKGROUND:Yes-associated protein (YAP), an essential component of Hippo pathway, was identified as an oncoprotein which participated in the progression of various malignancies. However, its role in chronic myeloid leukemia (CML) remains to be further clarified. METHODS:The expression of YAP in CML cells was determine...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-016-0414-z
更新日期:2016-09-06 00:00:00
abstract:BACKGROUND:Dysregulated endocytosis of membrane proteins contributes significantly to several hallmarks of cancer. Basigin can enhance cancer progression, but its precise mechanism remains unclear. CD98 promotes cell spreading and tumorigenicity by triggering integrin clustering and enhancing cell adhesion to the extra...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-015-0226-6
更新日期:2015-10-06 00:00:00
abstract::We evaluated the efficacy and toxicity profile of single-agent docetaxel administered in daily clinical practice at low-dose regimen in 37 pre-treated elderly patients with metastatic breast cancer previously exposed to chemotherapy. Docetaxel was employed by physician's preference according to a weekly (8 patients, 2...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 临床试验,杂志文章
doi:
更新日期:2005-03-01 00:00:00
abstract:BACKGROUND:Dendritic cells (DCs) have been used successfully in clinical pilot studies. However, tumor-specific immunity and clinical responses were only induced in certain cancer patients. It has been well documented that immunotherapy efficacy can be optimized for responses using antigen pulsing. METHODS:The human l...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-016-0295-1
更新日期:2016-01-22 00:00:00
abstract:BACKGROUND:Accumulating evidences indicated that lncRNAs play crucial regulatory roles in oncogenesis and progression of cancers. BRAF activated non-coding RNA (BANCR) has been identified to contribute to the progression of some human cancers. However, the relationship between BANCR and bladder cancer (BC) is largely u...
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::The aim of this work is the in vitro study of the late effects of single proton irradiation on HTB63 human melanoma cell growth, cell cycle and cell death. The experimental conditions were focused on analyzing the effects of irradiation on the periphery of tumour that can be, in clinical practice, close to critical or...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2001-03-01 00:00:00
abstract:BACKGROUND:m6A modification has been proved to play an important role in many biological processes. METTL3 as the main methyltransferase for methylation process has been found to be upregulated in many cancers, including CRC. Here, we investigate m6A modification and the underlying mechanism of METTL3 in the developmen...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-019-1408-4
更新日期:2019-09-06 00:00:00
abstract::In the original publication of this manuscript [1], Fig. 5E lower panel was incorrect due to an error in the preparation of these figures for publication. It was noticed that in the lower panel of Fig. 5E, one mouse image of ApoE-/- + PBS group (upper) was a photograph coming from ApoE-/- + BAPN pre-treatment group (l...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 已发布勘误
doi:10.1186/s13046-019-1422-6
更新日期:2019-10-15 00:00:00
abstract::Distant metastases (DM) is the point of concern and seems to be on the rise with the improved control of the laryngeal cancer in the primary site and neck regions. Prognostic factors must be evaluated to improve the detection of DM at early stage of the disease. Therefore, we have analyzed our cases of laryngeal squam...
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
abstract:BACKGROUND:New chemotherapic agents and new protocols in oncology have led to an increasing survival rate in patients affected by tumors. However, this increased use has been accompanied by a growth in the incidence of cutaneous side effects and a worsening of patients' quality of life. Appropriate management of skin t...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-31-50
更新日期:2012-05-28 00:00:00