The role of WWOX tumor suppressor gene in the regulation of EMT process via regulation of CDH1-ZEB1-VIM expression in endometrial cancer.

Abstract:

:This study defines the role of WWOX in the regulation of epithelial to mesenchymal transition. A group of 164 endometrial adenocarcinoma patients was studied as well as an ECC1 well-differentiated steroid-responsive endometrial cell line, which was transducted with WWOX cDNA by a retroviral system. The relationship between WWOX gene and EMT marker (CDH1, VIM, ZEB1, SNAI1) expression on mRNA (RT-qPCR) and protein levels (western blotting) was evaluated. The EMT processes were also analysed in vitro by adhesion of cells to extracellular matrix proteins, migration through a basement membrane, anchorage-independent growth and MMP activity assay. DNA microarrays (HumanOneArray™) were used to determine WWOX-dependent pathways in an ECC1 cell line. A positive correlation was observed between WWOX and ZEB1, and a negative correlation between CDH1 and VIM. WWOX expression was found to inversely correlate with the risk of recurrence of tumors in patients. However, in the WWOX-expressing ECC1 cell line, WWOX expression was found to be inversely related with VIM and positively with CDH1. The ECC1/WWOX cell line variant demonstrated increased migratory capacity, with increased expression of metalloproteinases MMP2/MMP9. However, these cells were not able to form colonies in suspension and revealed decreased adhesion to fibronectin and fibrinogen. Microarray analysis demonstrated that WWOX has an impact on the variety of cellular pathways including the cadherin and integrin signalling pathways. Our results suggest that the WWOX gene plays a role in the regulation of EMT processes in endometrial cancer by controlling the expression of proteins associated with cell motility, thus influencing tissue remodeling, with the suppression of mesenchymal markers.

journal_name

Int J Oncol

authors

Płuciennik E,Nowakowska M,Pospiech K,Stępień A,Wołkowicz M,Gałdyszyńska M,Popęda M,Wójcik-Krowiranda K,Bieńkiewicz A,Bednarek AK

doi

10.3892/ijo.2015.2964

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

2639-48

issue

6

eissn

1019-6439

issn

1791-2423

journal_volume

46

pub_type

杂志文章
  • Imbalance between cathepsin-B and cysteine proteinase-inhibitors is of prognostic-significance in human lung-cancer.

    abstract::In the study of 69 matched pairs of lung tumors and normal lung parenchyma, the median activities of cathepsin B (CB) and cystein proteinase inhibitors (CPI's) in tumors were found to be increased 4.4-fold and twofold, respectively. The levels of CB and CPI activities did not correlate with TNM stages nor with cell di...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.5.1.77

    authors: Knoch H,Werle B,Ebert W,Spiess E

    更新日期:1994-07-01 00:00:00

  • HIF1-positive and HIF1-negative glioblastoma cells compete in vitro but cooperate in tumor growth in vivo.

    abstract::Glioblastoma multiforme (GBM) is characterized by extensive angiogenesis that is mostly orchestrated by the hypoxia inducible factor HIF-1. Deregulation of HIF-1 is believed to contribute to cancer initiation and progression. However, instances have been described in which loss of HIF-1 leads to more aggressive tumors...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo_00000554

    authors: Fiorenzo P,Mongiardi MP,Dimitri D,Cozzolino M,Ferri A,Montano N,Trevisi G,Maira G,Battistini L,Falchetti ML,Levi A,Pallini R

    更新日期:2010-04-01 00:00:00

  • Increased malignant behavior in neuroblastoma cells with acquired multi-drug resistance does not depend on P-gp expression.

    abstract::Acquisition of P-gp-mediated multidrug-resistance does not always correlate with observed malignant behavior of NB. To characterize alterations accompanying development of multidrug-resistance in NB we established two neuroblastoma cell sublines resistant to vincristine (UKF-NB-3rVCR10) and doxorubicin (UKF-NB-3rDOX20...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Kotchetkov R,Driever PH,Cinatl J,Michaelis M,Karaskova J,Blaheta R,Squire JA,Von Deimling A,Moog J,Cinatl J Jr

    更新日期:2005-10-01 00:00:00

  • Autoantibodies against insulin-like growth factor‑binding protein-2 as a serological biomarker in the diagnosis of lung cancer.

    abstract::Insulin-like growth factor-binding protein-2 (IGFBP-2) is considered to be a human tumor antigen, and the tumor-specific immunity of IGFBP-2 has been reported in several types of cancer. The purpose of this study was to evaluate whether autoantibodies to IGFBP-2 can be used as diagnostic markers in lung cancer. The re...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2012.1699

    authors: Zhang Y,Ying X,Han S,Wang J,Zhou X,Bai E,Zhang J,Zhu Q

    更新日期:2013-01-01 00:00:00

  • Correlation between the immunohistochemical and mRNA expression of glutathione S-transferase-pi and cisplatin plus etoposide chemotherapy response in patients with untreated primary non-small cell lung cancer.

    abstract::Patients who have inoperable lung cancer usually undergo chemotherapy and have problems such as a resistance against chemotherapeutic agents during the treatment. Glutathione S-transferase (GST) is one of the detoxication-related enzymes. We studied the relationship between immunohisto-chemical staining of GST-pi type...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.11.1.127

    authors: Arai T,Yasuda Y,Takaya T,Yoshimi N,Ito H,Fujiwara H

    更新日期:1997-07-01 00:00:00

  • Resistance factors and proliferative activity in childhood acute nonlymphoblastic leukemia.

    abstract::Thirty-four children with newly diagnosed acute nonlymphoblastic leukemia were analysed for the expression of P-glycoprotein (P-170), glutathione S-transferase-pi, (GST-pi) topoisomerase II (Topo II) and the proliferation antigen Ki-67 by the streptavidin-biotin-peroxidase method. Overexpression of P-170 was present i...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.5.4.841

    authors: Sauerbrey A,Zintl F,Volm M

    更新日期:1994-10-01 00:00:00

  • Inhibition of b16 melanoma metastasis by administration of g(m3)- or gg3- liposomes - blocking adhesion of melanoma-cells to endothelial-cells (antiadhesion therapy) via inhibition of g(m3)-gg3cer or g(m3)-laccer interaction.

    abstract::Tumor cell (TC) metastasis is initiated by selective adhesion of TCs to target structures such as basement membrane and endotheliaI cells (ECs), followed by transvascular migration of TCs. Variants of murine B16 melanoma having different metastatic potentials (in the order BL6 greater than or equal to F10>F1>WA4) have...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.6.2.319

    authors: Otsuji E,Park Y,Tashiro K,Kojima N,Toyokuni T,Hakomori S

    更新日期:1995-02-01 00:00:00

  • DNA binding protein A expression and methylation status in hepatocellular carcinoma and the adjacent tissue.

    abstract::We investigated the expression and promoter methylation of dbpA in human hepatocellular carcinoma (HCC) and examined their correlation with clinicopathological features. In 96 paired samples of HCC and adjacent non-tumorous liver, and 10 normal liver specimens, dbpA mRNA was quantif...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2011.1282

    authors: Yasen M,Obulhasim G,Kajino K,Mogushi K,Mizushima H,Tanaka S,Tanaka H,Hino O,Arii S

    更新日期:2012-03-01 00:00:00

  • How surgeon age affects post-treatment surveillance strategies for melanoma patients.

    abstract::The intensity of post-treatment melanoma patient follow-up varies widely among physicians. We investigated whether physician age accounts for the observed variation in surveillance intensity among plastic surgeons. A custom-designed questionnaire was mailed to USA and non-USA surgeons, all of whom were members of the ...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.19.1.175

    authors: Margenthaler JA,Virgo KS,Johnson DY,Sugarbaker EM,Handler BS,Johnson FE

    更新日期:2001-07-01 00:00:00

  • Aspirin induces apoptosis in vitro and inhibits tumor growth of human hepatocellular carcinoma cells in a nude mouse xenograft model.

    abstract::Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to induce apoptosis in a variety of cancer cells, including colon, prostate, breast and leukemia. Among them, aspirin, a classical NSAID, shows promise in cancer therapy in certain types of cancers. We hypothesized that aspirin...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2011.1304

    authors: Hossain MA,Kim DH,Jang JY,Kang YJ,Yoon JH,Moon JO,Chung HY,Kim GY,Choi YH,Copple BL,Kim ND

    更新日期:2012-04-01 00:00:00

  • Down-regulation of FAK and IAPs by laminin during cisplatin-induced apoptosis in testicular germ cell tumors.

    abstract::The purpose of this present study was to investigate the role of inhibitor of apoptosis proteins (IAPs), their inhibitor, Smac, and the focal adhesion kinase (FAK) in the laminin enhancement of cisplatin-induced apoptosis in a testicular tumor germ cell line, NCCIT. We demonstrated that specifically in laminin-adheren...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Andjilani M,Droz JP,Benahmed M,Tabone E

    更新日期:2006-02-01 00:00:00

  • An in vivo tumor model expressing green fluorescent protein for the investigation of metastasis.

    abstract::Although strong evidence is available suggesting that microenvironmental parameters play a role in lymphogenic or hematogenic metastasis, the underlying mechanisms are still unclear and further investigations of this topic are needed. For such a study however, an appropriate model of metastasis for in vivo analysis of...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Thews O,Lambert C,Kelleher DK,Biesalski HK,Vaupel P,Frank J

    更新日期:2005-09-01 00:00:00

  • Bmi1 knockdown inhibits hepatocarcinogenesis.

    abstract::Although Bmi1 is well established as one of the most commonly activated oncogenes, the precise role of Bmi1 during hepatocarcinogenesis remains unclear. In addition, Bmi1 provides a potential therapeutic target for the future treatment of hepatocellular carcinoma (HCC). In this stud...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2012.1693

    authors: Ruan ZP,Xu R,Lv Y,Tian T,Wang WJ,Guo H,Nan KJ

    更新日期:2013-01-01 00:00:00

  • Mechanisms underlying resistance to cetuximab in the HNSCC cell line: role of AKT inhibition in bypassing this resistance.

    abstract::EGFR is frequently overexpressed in head and neck squamous cell cancer (HNSCC). Cetuximab is a monoclonal antibody designed to interact with EGFR, block its activation, reduce the downstream signaling pathways and induce EGFR internalization. This study aims to investigate the role of the EGFR signaling pathway and EG...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Rebucci M,Peixoto P,Dewitte A,Wattez N,De Nuncques MA,Rezvoy N,Vautravers-Dewas C,Buisine MP,Guerin E,Peyrat JP,Lartigau E,Lansiaux A

    更新日期:2011-01-01 00:00:00

  • Transcriptomic study of dormant gastrointestinal cancer stem cells.

    abstract::We previously discovered the coexistence of dormant and proliferating cancer stem cells (CSCs) in gastrointestinal cancer, which leads to chemoradiation resistance. CD13-/CD90+ proliferating liver CSCs are sensitive to chemotherapy, and CD13+/CD90- dormant CSCs have a limited prolif...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2012.1531

    authors: Nishikawa S,Dewi DL,Ishii H,Konno M,Haraguchi N,Kano Y,Fukusumi T,Ohta K,Noguchi Y,Ozaki M,Sakai D,Satoh T,Doki Y,Mori M

    更新日期:2012-09-01 00:00:00

  • DLC1 suppresses distant dissemination of human hepatocellular carcinoma cells in nude mice through reduction of RhoA GTPase activity, actin cytoskeletal disruption and down-regulation of genes involved in metastasis.

    abstract::The process of cell dissemination from the primary tumors to distant sites is the most harmful event during cancer progression, and the leading cause of cancer death. We have previously demonstrated that restoration of DLC1 tumor suppressor gene expression in the DLC1-negative Focus and 7703K human hepatocellular carc...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo_32_6_1285

    authors: Zhou X,Zimonjic DB,Park SW,Yang XY,Durkin ME,Popescu NC

    更新日期:2008-06-01 00:00:00

  • Establishment and characterization of a novel cell line (cc‑006cpm8) of moderately/poorly differentiated colorectal adenocarcinoma derived from a primary tumor of a patient.

    abstract::In the present study, the cc‑006cpm8 novel colon cell line was established from a sample of right colorectal adenocarcinoma obtained from a woman with liver metastasis. It was possible to culture this cell line for ≥100 passages in vitro with vigorous growth. Morphologically, the cells grew as several layers with tigh...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2019.4806

    authors: Chu X,Xue Y,Huo X,Wei J,Chen Y,Han R,Chen H,Su X,Zhang H,Gong Y,Chen J

    更新日期:2019-07-01 00:00:00

  • Recapitulation of a normal cellular growth program in early invasive breast-cancer.

    abstract::With a view to identifying markers reflecting not the evidence of, but the potential for, neoplastic progression of the breast we have compared the normal invasive mammary epithelial cell growth seen at puberty with invasive and non-invasive carcinogenesis using the mouse as a model. We have analyzed cell proliferatio...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Djonov V,Altermatt H,Arnold A,Gerber H,Andres A

    更新日期:1995-08-01 00:00:00

  • DKK3 knockdown confers negative effects on the malignant potency of head and neck squamous cell carcinoma cells via the PI3K/Akt and MAPK signaling pathways.

    abstract::Dickkopf‑related protein 3 (DKK3), which is a member of the Dickkopf WNT signaling pathway inhibitor family, is considered to be a tumor suppressor, due to its reduced expression in cancer cells and its ability to induce apoptosis when overexpressed by adenovirus. However, our previous study demonstrated alternative f...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2018.4667

    authors: Katase N,Nishimatsu SI,Yamauchi A,Yamamura M,Fujita S

    更新日期:2019-03-01 00:00:00

  • Fibrous tumors in children - a morphologic and interphase cytogenetic analysis of problematic cases.

    abstract::We describe and discuss the findings by fluorescent in situ hybridization (FISH) for detection of non-random chromosomal gains, in a group of unusual fibrous lesions in children. Nuclear disaggregation was used to prepare slides from eight cases which were hybridized using alpha-satellite enumeration probes for chromo...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.17.3.433

    authors: Flores-Stadler EM,Chou PM,Barquin N,Thangavelu M,Gonzalez-Crussi F

    更新日期:2000-09-01 00:00:00

  • Human non‑small cell lung cancer cells can be sensitized to camptothecin by modulating autophagy.

    abstract::Lung cancer is a prevalent disease and is one of the leading causes of mortality worldwide. Despite the development of various anticancer drugs, the prognosis of lung cancer is relatively poor. Metastasis of lung cancer, as well as chemoresistance, is associated with a high mortality rate for patients with lung cancer...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2018.4523

    authors: Chiu YH,Hsu SH,Hsu HW,Huang KC,Liu W,Wu CY,Huang WP,Chen JY,Chen BH,Chiu CC

    更新日期:2018-11-01 00:00:00

  • Genomic characterization of five commonly used endometrial cancer cell lines.

    abstract::Recently, the compilation of massive amounts of genetic and genomic information on a wide variety of human cancer types, collectively known as The Cancer Genome Atlas (TCGA), has revealed a wealth of descriptive classification schemes both within and between different types and sources of cancer. In endometrial cancer...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2020.5139

    authors: Devor EJ,Gonzalez-Bosquet J,Thiel KW,Leslie KK

    更新日期:2020-12-01 00:00:00

  • Prevalent hyper-methylation of the CDH13 gene promoter in malignant B cell lymphomas.

    abstract::CDH13 (H-cadherin) is a member of the cadherin superfamily, which plays an important role in cell recognition and adhesion. We examined the expression and methylation status of the CDH13 gene in diffuse large B cell lymphomas (B-DLCLs). We found decreased expression of the CDH13 gene in all of 6 hematopoietic cell lin...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Ogama Y,Ouchida M,Yoshino T,Ito S,Takimoto H,Shiote Y,Ishimaru F,Harada M,Tanimoto M,Shimizu K

    更新日期:2004-09-01 00:00:00

  • Allelic imbalance and microsatellite instability in plasma DNA released from polyclonal pancreatic adenocarcinoma.

    abstract::Evidence of circulating soluble DNA in blood-stream of cancer patients has emerged. Because the plasma DNA is largely derived from cancer cells, genetic analysis of plasma DNA is important to understand the molecular events occurred in cancer patient. Seven microsatellite markers in the soluble plasma DNA from patient...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.21.5.949

    authors: Moriyama H,Matsubara N,Kanbara T,Mori M,Matsuoka J,Yoshino T,Takakura N,Shimizu K,Takaka N

    更新日期:2002-11-01 00:00:00

  • Increased interleukin-17A levels promote rituximab resistance by suppressing p53 expression and predict an unfavorable prognosis in patients with diffuse large B cell lymphoma.

    abstract::Rituximab resistance has become increasingly common in patients with diffuse large B cell lymphoma (DLBCL). However, the mechanisms involved remain unclear. In this study, we aimed to examine the effect of rituximab on interleukin (IL)-17A and to investigate the role of IL-17A in rituximab resistance and its prognosti...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2018.4299

    authors: Zhong W,Xu X,Zhu Z,Yang L,Du H,Xia Z,Yuan Z,Xiong H,Du Q,Wei Y,Li Q

    更新日期:2018-05-01 00:00:00

  • Colonic prostaglandin-e2 in carcinogenesis in rats with N-methyl-n'-nitrosoguanidine.

    abstract::The effects of prostaglandin E2 and indomethacin on carcinogenesis were studied in male Wistar rats. Of the rats, those treated with MNNG (MNNG group) were given 1 ml of 0.1% solution of MNNG in distilled water by intrarectal instillation every day for 14 days. The diet for the rats treated with Indomethacin and MNNG ...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Yamaguchi A,Goi T,Nakagawara G,Ishida T,Miyazaki I

    更新日期:1993-08-01 00:00:00

  • miR-145 inhibits breast cancer cell growth through RTKN.

    abstract::MicroRNAs (miRNAs) represent a class of small non-coding RNAs regulating gene expression by inducing RNA degradation or interfering with translation. Aberrant miRNA expression has been described for several human malignancies. Herein, we show that miR-145 is down-regulated in human cancer cell line MCF-7 when compared...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Wang S,Bian C,Yang Z,Bo Y,Li J,Zeng L,Zhou H,Zhao RC

    更新日期:2009-05-01 00:00:00

  • Screening of mammalian DNA polymerase and topoisomerase inhibitors from Garcinia mangostana L. and analysis of human cancer cell proliferation and apoptosis.

    abstract::We purified and identified eight xanthones from mangosteen (Garcinia mangostana L.) and investigated whether these compounds inhibited the activities of mammalian DNA polymerases (Pols) and human DNA topoisomerases (Topos). β-Mangostin was the strongest inhibitor of both mammalian Pols and human Topos among the isolat...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2016.3321

    authors: Onodera T,Takenaka Y,Kozaki S,Tanahashi T,Mizushina Y

    更新日期:2016-03-01 00:00:00

  • (-)-Epigallocatechin 3-gallate inhibits invasion by inducing the expression of Raf kinase inhibitor protein in AsPC‑1 human pancreatic adenocarcinoma cells through the modulation of histone deacetylase activity.

    abstract::The aim of the present study was to assess whether (-)-epigallocatechin 3-gallate (EGCG) via epigenetic modifications, regulates Raf kinase inhibitor protein (RKIP) expression and invasive metastatic activity in AsPC-1 pancreatic adenocarcinoma cells. Basal levels of RKIP were examined in various human pancreatic canc...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2012.1686

    authors: Kim SO,Kim MR

    更新日期:2013-01-01 00:00:00

  • Expression and potential function of the CXC chemokine CXCL16 in pancreatic ductal adenocarcinoma.

    abstract::CXC chemokines have a major influence on the angiogenesis, growth and metastatic potential of pancreatic ductal adenocarcinoma. CXCL16 is a unique transmembrane CXC chemokine, which is shed by members of the disintegrins and metalloproteases (ADAMs), in particular by ADAM10 and ADAM17. In our study, we evaluated expre...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Wente MN,Gaida MM,Mayer C,Michalski CW,Haag N,Giese T,Felix K,Bergmann F,Giese NA,Friess H

    更新日期:2008-08-01 00:00:00