MAZ promotes prostate cancer bone metastasis through transcriptionally activating the KRas-dependent RalGEFs pathway.

Abstract:

BACKGROUND:Clinically, prostate cancer (PCa) exhibits a high avidity to metastasize to bone. Myc-associated zinc-finger protein (MAZ) is a well-documented oncogene involved in the progression and metastasis of multiple cancer types, even in PCa. However, the clinical significance and biological roles of MAZ in bone metastasis of PCa remain unclear. METHODS:MAZ expression was examined in PCa tissues with bone metastasis, PCa tissues without bone metastasis and metastatic bone tissues by real-time PCR and immunohistochemistry (IHC), respectively. Statistical analysis was performed to evaluate the clinical correlation between MAZ expression and clinicopathological features and bone metastasis-free survival in PCa patients. Biological roles of MAZ in bone metastasis of PCa were investigated both in vitro by transwell assay, and in vivo by a mouse model of left cardiac ventricle inoculation. The bioinformatics analysis, western blot, pull-down assays, chromatin immunoprecipitation (ChIP) and luciferase reporter assays were applied to demonstrate and examine the relationship between MAZ and its potential downstream signalling pathway. TaqMan copy number assay was performed to identify the underlying mechanism responsible for MAZ overexpression in PCa tissues. RESULTS:MAZ expression is elevated in PCa tissues with bone metastasis compared with that in PCa tissues without bone metastasis, and is further increased in metastatic bone tissues. High expression of MAZ positively correlates with poor overall and bone metastasis-free survival in PCa patients. Upregulating MAZ elevates, while silencing MAZ represses the invasion and migration abilities of PCa cells in vitro and bone metastasis ability in vivo. Our results further reveal that MAZ promotes bone metastasis of PCa dependent on KRas signalling, although MAZ transcriptionally upregulates KRas and HRas expression, where the Ral guanine nucleotide exchange factor (RalGEF) signaling is responsible for the different roles of KRas and HRas in mediating the pro-bone metastasis of MAZ in PCa. Finally, our results indicate that recurrent gains contribute to MAZ overexpression in a small portion of PCa tissues. CONCLUSION:These results indicate that the MAZ/Kras/ RalGEF signalling axis plays a crucial role in promoting PCa cell bone metastasis, suggesting a potential therapeutic utility of MAZ in bone metastasis of PCa.

journal_name

J Exp Clin Cancer Res

authors

Yang Q,Lang C,Wu Z,Dai Y,He S,Guo W,Huang S,Du H,Ren D,Peng X

doi

10.1186/s13046-019-1374-x

subject

Has Abstract

pub_date

2019-09-05 00:00:00

pages

391

issue

1

eissn

0392-9078

issn

1756-9966

pii

10.1186/s13046-019-1374-x

journal_volume

38

pub_type

杂志文章
  • Oncogene addiction in gliomas: implications for molecular targeted therapy.

    abstract::Oncogene addiction is a phenomenon that the survival of cancer cells depends on an activated oncogene or inactivation of tumor suppressor gene, and is regarded as the 'Achilles heel' of the successful molecular targeted therapies in cancer. However, the role of oncogene addiction in gliomas has not been elucidated sys...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章,评审

    doi:10.1186/1756-9966-30-58

    authors: Yan W,Zhang W,Jiang T

    更新日期:2011-05-17 00:00:00

  • Single nucleotide polymorphisms in the mitochondrial displacement loop and outcome of esophageal squamous cell carcinoma.

    abstract:BACKGROUND:Accumulation of single nucleotide polymorphisms (SNPs) in the displacement loop (D-loop) of mitochondrial DNA (mtDNA) has been described for different types of cancers and might be associated with cancer risk and disease outcome. We used a population-based series of esophageal squamous cell carcinoma (ESCC) ...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/1756-9966-29-155

    authors: Zhang R,Wang R,Zhang F,Wu C,Fan H,Li Y,Wang C,Guo Z

    更新日期:2010-11-26 00:00:00

  • Anti-tumour effects of all-trans retinoid acid on serous ovarian cancer.

    abstract:BACKGROUND:Annexin A2 is increased in serous ovarian cancer and plays an essential role in ovarian cancer invasion and metastasis. In combination with S100A10, annexin A2 plays an important role in the plasminogen activator system regulating plasmin production. The aim of this study was to investigate the potential uti...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/s13046-018-1017-7

    authors: Lokman NA,Ho R,Gunasegaran K,Bonner WM,Oehler MK,Ricciardelli C

    更新日期:2019-01-08 00:00:00

  • SNPs in DNA repair or oxidative stress genes and late subcutaneous fibrosis in patients following single shot partial breast irradiation.

    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

    authors: Falvo E,Strigari L,Citro G,Giordano C,Boboc G,Fabretti F,Bruzzaniti V,Bellesi L,Muti P,Blandino G,Pinnarò P

    更新日期:2012-01-24 00:00:00

  • Role of retinoic receptors in lung carcinogenesis.

    abstract::Several in vitro and in vivo studies have examined the positive and negative effects of retinoids (vitamin A analogs) in premalignant and malignant lesions. Retinoids have been used as chemopreventive and anticancer agents because of their pleiotropic regulator function in cell differentiation, growth, proliferation a...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章,评审

    doi:10.1186/1756-9966-27-18

    authors: Bogos K,Renyi-Vamos F,Kovacs G,Tovari J,Dome B

    更新日期:2008-07-14 00:00:00

  • Inhibition of SOX2 induces cell apoptosis and G1/S arrest in Ewing's sarcoma through the PI3K/Akt pathway.

    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

    authors: Ren C,Ren T,Yang K,Wang S,Bao X,Zhang F,Guo W

    更新日期:2016-03-11 00:00:00

  • Influence of time interval between surgery and radiotherapy on tumor regrowth.

    abstract:UNLABELLED:In order to evaluate the influence of time intervals between tumor cell injection and radiotherapy on tumor control and regrowth after surgery, we performed two kinds of experiments on C3D2F1 mice bearing a mammary carcinoma inoculated in the foot or leg. 1st experiment: tumor in foot. END POINT:Tumor Contr...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:

    authors: Cividalli A,Creton G,Ceciarelli F,Strigari L,Tirindelli Danesi D,Benassi M

    更新日期:2005-03-01 00:00:00

  • Loss of expression of Kruppel-like factor 6 in primary hepatocellular carcinoma and hepatoma cell lines.

    abstract::KLF6 (Zf9, COPEB), an ubiquitous transcription factor, maps to chromosome 10p. Recently, KLF6 was found to have a more generalized role in tumorigenesis as a candidate tumor suppressor gene for some tumors. However, results from other published studies seem not to be in agreement with data from previous studies. Gene-...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:

    authors: Wang SP,Zhou HJ,Chen XP,Ren GY,Ruan XX,Zhang Y,Zhang RL,Chen J

    更新日期:2007-03-01 00:00:00

  • A pilot study on the impact of known drug-drug interactions in cancer patients.

    abstract:BACKGROUND:When a patient concomitantly uses two or more drugs, a drug-drug interaction (DDI) can possibly occur, potentially leading to an increased or decreased clinical effect of a given treatment. Cancer patients are at high risk of such interactions because they commonly receive multiple medications. Moreover, mos...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/s13046-015-0201-2

    authors: Ussai S,Petelin R,Giordano A,Malinconico M,Cirillo D,Pentimalli F

    更新日期:2015-08-25 00:00:00

  • CCDC88A, a prognostic factor for human pancreatic cancers, promotes the motility and invasiveness of pancreatic cancer cells.

    abstract:BACKGROUND:Coiled-Coil Domain Containing 88A (CCDC88A) was identified as a substrate of the serine/threonine kinase Akt that is capable of binding to the actin cytoskeleton. The aim of this study was to investigate the potential role of CCDC88A in the migration and invasiveness of pancreatic ductal adenocarcinoma (PDAC...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/s13046-016-0466-0

    authors: Tanouchi A,Taniuchi K,Furihata M,Naganuma S,Dabanaka K,Kimura M,Watanabe R,Kohsaki T,Shimizu T,Saito M,Hanazaki K,Saibara T

    更新日期:2016-12-05 00:00:00

  • In vitro antineoplastic effects of brivaracetam and lacosamide on human glioma cells.

    abstract:BACKGROUND:Epilepsy is a frequent symptom in patients with glioma. Although treatment with antiepileptic drugs is generally effective in controlling seizures, drug-resistant patients are not uncommon. Multidrug resistance proteins (MRPs) and P-gp are over-represented in brain tissue of patients with drug-resistant epil...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/s13046-017-0546-9

    authors: Rizzo A,Donzelli S,Girgenti V,Sacconi A,Vasco C,Salmaggi A,Blandino G,Maschio M,Ciusani E

    更新日期:2017-06-06 00:00:00

  • An embryo-specific expressing TGF-β family protein, growth-differentiation factor 3 (GDF3), augments progression of B16 melanoma.

    abstract::Malignant tumor cells often express embryonic antigens which share the expression with embryonic stem (ES) cells. The embryonic antigens are usually encoded by ES cell-specific genes, a number of which are associated with tumorigenesis and/or tumor progression. We examined the expression of ES cell-specific genes in t...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/1756-9966-29-135

    authors: Ehira N,Oshiumi H,Matsumoto M,Kondo T,Asaka M,Seya T

    更新日期:2010-10-15 00:00:00

  • The immunoregulatory mechanisms of carcinoma for its survival and development.

    abstract::The immune system in patients detects and eliminates tumor cells, but tumors still progress persistently. The mechanisms by which tumor cells survive under the pressure of immune surveillance are not fully understood. This review is to present the evidence from clinical studies, showing a significant correlation of cl...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章,评审

    doi:10.1186/1756-9966-30-12

    authors: Du C,Wang Y

    更新日期:2011-01-21 00:00:00

  • Retraction Note: Long noncoding RNA MLK7-AS1 promotes ovarian cancer cells progression by modulating miR-375/YAP1 axis.

    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: 已发布勘误,撤回出版物

    doi:10.1186/s13046-020-01746-0

    authors: Yan H,Li H,Li P,Li X,Lin J,Zhu L,Silva MA,Wang X,Wang P,Zhang Z

    更新日期:2020-11-05 00:00:00

  • LncRNA XIST/miR-34a axis modulates the cell proliferation and tumor growth of thyroid cancer through MET-PI3K-AKT signaling.

    abstract:BACKGROUND:Thyroid cancer is one of the most prevalent malignancies in endocrine system. Further understanding and revealing the molecular mechanism underlying thyroid cancer are indispensable for the development of effective diagnosis and treatments. In the present study, we attempted to provide novel basis for target...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/s13046-018-0950-9

    authors: Liu H,Deng H,Zhao Y,Li C,Liang Y

    更新日期:2018-11-21 00:00:00

  • Reduction of lung metastasis, cell invasion, and adhesion in mouse melanoma by statin-induced blockade of the Rho/Rho-associated coiled-coil-containing protein kinase pathway.

    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

    authors: Kidera Y,Tsubaki M,Yamazoe Y,Shoji K,Nakamura H,Ogaki M,Satou T,Itoh T,Isozaki M,Kaneko J,Tanimori Y,Yanae M,Nishida S

    更新日期:2010-09-16 00:00:00

  • Correction to: Liquid biopsy and tumor heterogeneity in metastatic solid tumors: the potentiality of blood samples.

    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,已发布勘误

    doi:10.1186/s13046-020-01615-w

    authors: Russano M,Napolitano A,Ribelli G,Iuliani M,Simonetti S,Citarella F,Pantano F,Dell'Aquila E,Anesi C,Silvestris N,Argentiero A,Solimando AG,Vincenzi B,Tonini G,Santini D

    更新日期:2020-06-24 00:00:00

  • Amelioration of cisplatin induced nephrotoxicity in mice by ethyl acetate extract of a polypore fungus, Phellinus rimosus.

    abstract::Pretreatment of ethyl acetate extract of Phellinus rimosus (Berk) Pilat protected cisplatin induced nephrotoxicity in mice. Single dose of the extract (25 and 50 mg/kg body weight) decreased cisplatin induced serum creatinine and urea levels. The cisplatin depleted renal antioxidant defence system, such as activity of...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:

    authors: Ajith TA,Jose N,Janardhanan KK

    更新日期:2002-06-01 00:00:00

  • Toxicity and morbility after isolated lower limb perfusion in 242 chemo-hyperthermal treatments for cutaneous melanoma: the experience of the Tuscan Reference Centre.

    abstract:BACKGROUND:The aim of this retrospective study was to assess the results concerning the regional and systemic toxicity and complications in 242 chemo-hyperthermal treatments (HILPs) for lower limb melanoma. PATIENTS AND METHODS:60 HILPs (G-A) were performed with mild HT plus L-PAM (10 mg/lt) +/- D-actimomycin; 74 HILP...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/1756-9966-27-67

    authors: Pace M,Gattai R,Matteini M,Mascitelli EM,Bechi P

    更新日期:2008-11-12 00:00:00

  • CpG oligonucleotides suppress HepG2 cells-induced Jurkat cell apoptosis via the Fas-FasL-mediated pathway.

    abstract:OBJECTIVE:To explore the potential role of CpG motif-containing oligonucleotides (CpG-ODN) in modulating the expression of FasL in HepG2 and Fas in Jurkat cells in vitro, and to examine the effect of CpG-ODN treatment on the HepG2 cells-mediated Jurkat cell apoptosis in vitro. METHODS:The expressions of FasL in HepG2 ...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/1756-9966-30-48

    authors: Zheng J,Fu R,Li J,Wang X

    更新日期:2011-05-03 00:00:00

  • Transcriptional and post-transcriptional controls of survivin in cancer cells: novel approaches for cancer treatment.

    abstract::Survivin is a novel member of the inhibitor of apoptosis (IAP) protein family, and its aberrant expression in cancer cells has been shown to be associated with tumorigenesis, cancer progression, radiation/drug resistance and shorter patient survival. Survivin is also expressed in certain human adult tissues and cells,...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章,评审

    doi:

    authors: Zhang M,Yang J,Li F

    更新日期:2006-09-01 00:00:00

  • microRNA-96 promotes occurrence and progression of colorectal cancer via regulation of the AMPKα2-FTO-m6A/MYC axis.

    abstract:BACKGROUND:Colorectal cancer (CRC) is one of the frequently occurred malignancies in the world. To date, several onco-microRNAs (miRNAs or miRs), including miR-96, have been identified in the pathogenesis of CRC. In the present study, we aimed to corroborate the oncogenic effect of miR-96 on CRC and to identify the spe...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/s13046-020-01731-7

    authors: Yue C,Chen J,Li Z,Li L,Chen J,Guo Y

    更新日期:2020-11-12 00:00:00

  • NR1B2 suppress kidney renal clear cell carcinoma (KIRC) progression by regulation of LATS 1/2-YAP signaling.

    abstract:BACKGROUND:Kidney Renal Clear Cell Carcinoma (KIRC) accounts for 75% of all renal cancers. Previous study had conflict evidences regarding NR1B2 role in cancer, and its expression and biological role in KIRC remained unclear. Our aims were to characterize the role of NR1B2 in KIRC. METHODS:NR1B2 expression in TCGA dat...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/s13046-019-1344-3

    authors: Yin L,Li W,Wang G,Shi H,Wang K,Yang H,Peng B

    更新日期:2019-08-07 00:00:00

  • Upregulation of lactate-inducible snail protein suppresses oncogene-mediated senescence through p16INK4a inactivation.

    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

    authors: Li X,Zhang Z,Zhang Y,Cao Y,Wei H,Wu Z

    更新日期:2018-02-26 00:00:00

  • Anti-HER-2 engineering antibody ChA21 inhibits growth and induces apoptosis of SK-OV-3 cells.

    abstract:BACKGROUND AND AIMS:Anti-HER-2 antibodies targeting distinct epitopes have different biological functions on cancer cells. In a previous study, we demonstrated that anti-HER-2 engineering antibody ChA21 was able to bind to subdomain I of HER-2 extracellular domain. In this study, The effects of ChA21 on growth and apop...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/1756-9966-29-23

    authors: Zhang A,Xue H,Ling X,Gao Y,Yang F,Cheng L,Liu J,Wu Q

    更新日期:2010-03-10 00:00:00

  • Regulation of tNOX expression through the ROS-p53-POU3F2 axis contributes to cellular responses against oxaliplatin in human colon cancer cells.

    abstract:BACKGROUND:Oxaliplatin belongs to the platinum-based drug family and has shown promise in treating cancer by binding to DNA to induce cytotoxicity. However, individual patients show diverse therapeutic responses toward oxaliplatin due to yet-unknown underlying mechanisms. We recently established that oxaliplatin also e...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/s13046-018-0837-9

    authors: Chen HY,Islam A,Yuan TM,Chen SW,Liu PF,Chueh PJ

    更新日期:2018-07-20 00:00:00

  • Synergistic anti-tumor effect of ultrasound and hematoporphyrin on sarcoma180 cells with special reference to the changes of morphology and cytochrome oxidase activity of tumor cells.

    abstract::This study is aimed at evaluating the inhibitory effects of the association of hematoporphyrin and ultrasound at variable intensities with a fixed frequency of 1.1MHz in tumor nodules. Specifically, the effects were studied both in solid and ascitic S180 tumors transplanted in mice by clinical, cytochemical and ultras...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:

    authors: Quan-hong L,Shi-hui S,Ya-ping X,Hao Q,Jin-xuan Z,Yao-hui R,Meng L,Pan W

    更新日期:2004-06-01 00:00:00

  • Annexin A2 contributes to cisplatin resistance by activation of JNK-p53 pathway in non-small cell lung cancer cells.

    abstract:BACKGROUND:Development of resistance to therapy continues to be a serious clinical problem in lung cancer management. We previously identified that Annexin A2 is significantly up-regulated in cisplatin-resistant non-small cell lung cancer (NSCLC) A549/DDP cells. However, the exact function and molecular mechanism of An...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:10.1186/s13046-017-0594-1

    authors: Feng X,Liu H,Zhang Z,Gu Y,Qiu H,He Z

    更新日期:2017-09-08 00:00:00

  • Combined effect of arsenic trioxide and sulindac sulfide in A549 human lung cancer cells in vitro.

    abstract::Arsenic trioxide has shown substantial efficacy in treating patients with relapsed or refractory acute promyelocytic leukemia (APL) as well as solid tumors. Arsenic can act through a considerable number of different pathways including mitochondrial respiration and tubulin formation, affecting growth, blood flow, diffe...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 杂志文章

    doi:

    authors: Jiang TT,Brown SL,Kim JH

    更新日期:2004-06-01 00:00:00

  • Correction to: Targeting hypoxia in tumor: a new promising therapeutic strategy.

    abstract::In the original publication of this manuscript [1], Fig. 1 contained a typographical error ('Metabolic' incorrectly written as 'Metabolig'). ...

    journal_title:Journal of experimental & clinical cancer research : CR

    pub_type: 已发布勘误

    doi:10.1186/s13046-020-1532-1

    authors: Bosco MC,Orazi G,Del Bufalo D

    更新日期:2020-02-24 00:00:00