ZIC2 is downregulated and represses tumor growth via the regulation of STAT3 in breast cancer.


:Although early detection and systemic therapies have improved the diagnosis and clinical cure rate of breast cancer, breast cancer remains the most frequently occurring malignant cancer in women due to a lack of sufficiently effective treatments. Thus, to develop potential targeted therapies and thus benefit more patients, it is helpful to understand how cancer cells work. ZIC family members have been shown to play important roles in neural development and carcinogenesis. In our study, we found that ZIC2 is downregulated in breast cancer tissues at both the mRNA and protein levels. Low expression of ZIC2 was correlated with poor outcome in breast cancer patients and serves as an independent prognostic marker. Furthermore, overexpression of ZIC2 repressed, whereas knockdown of ZIC2 promoted, cell proliferation and colony formation ability in vitro and tumor growth in vivo. Using ChIP-seq and RNA-seq analysis, we screened and identified STAT3 as a potential target for ZIC2. ZIC2 bound to the STAT3 promoter and repressed the promoter activities of STAT3. ZIC2 knockdown induced the expression of STAT3, increasing the level of phosphorylated STAT3. These results suggest that ZIC2 regulates the transcription of STAT3 by directly binding to the STAT3 promoter. Additionally, interfering STAT3 with siRNAs or inhibitors abrogated the oncogenic effects induced by decreased ZIC2. Taken together, our results indicate that ZIC2 serves as a useful prognostic marker in breast cancer and acts as a tumor suppressor by regulating STAT3, implying that STAT3 inhibitors might provide an alternative treatment option for breast cancer patients with ZIC2 downregulation.


Int J Cancer


Liu ZH,Chen ML,Zhang Q,Zhang Y,An X,Luo YL,Liu XM,Liu SX,Liu Q,Yang T,Liu YM,Liu BL,Zhou AJ,Li MZ,Liu YJ,Liu ZX,Zhong Q




Has Abstract


2020-07-15 00:00:00












  • Apoptotic body-loaded dendritic cells efficiently cross-prime cytotoxic T lymphocytes specific for NA17-A antigen but not for Melan-A/MART-1 antigen.

    abstract::DCs hold promise for cancer immunotherapy due to their functional ambivalence: iDCs internalize antigens, then mDCs trigger naive T-cell activation. However, no consensus has been reached concerning the optimal mode of antigen acquisition for efficient cross-priming of TAA-specific CTLs, and this remains a field of in...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Labarrière N,Bretaudeau L,Gervois N,Bodinier M,Bougras G,Diez E,Lang F,Gregoire M,Jotereau F

    更新日期:2002-09-20 00:00:00

  • Mantle cell lymphomas with low levels of cyclin D1 long mRNA transcripts are highly proliferative and can be discriminated by elevated cyclin A2 and cyclin B1.

    abstract::The role of transcript variants of cyclin D1 in cancer biology is unclear. Most tumors with high levels of cyclin D1 express 2 transcripts due to alternative splicing: one full-length transcript of 4.4 kb and one short transcript of approximately 1.7 kb. The short transcript lacks part of the 3'UTR region regulating m...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Sander B,Flygare J,Porwit-Macdonald A,Smith CI,Emanuelsson E,Kimby E,Liden J,Christensson B

    更新日期:2005-11-10 00:00:00

  • BYL719, a new α-specific PI3K inhibitor: single administration and in combination with conventional chemotherapy for the treatment of osteosarcoma.

    abstract::It has been established that disturbances in intracellular signaling pathways play a considerable part in the oncologic process. Phosphatidylinositol-3-kinase (PI3K) has become of key interest in cancer therapy because of its high mutation frequency and/or gain in function of its catalytic subunits in cancer cells. We...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Gobin B,Huin MB,Lamoureux F,Ory B,Charrier C,Lanel R,Battaglia S,Redini F,Lezot F,Blanchard F,Heymann D

    更新日期:2015-02-15 00:00:00

  • Screening for familial and hereditary prostate cancer.

    abstract::Prostate cancer (PC) has the highest degree of genetic transmission of any form of malignancy. In some families, the hereditary pattern is so strong as to mimic an autosomal dominance trait. We reviewed the known predisposing genetic markers to assess possible strategies for screening of families at risk. We carried o...

    journal_title:International journal of cancer

    pub_type: 杂志文章,评审


    authors: Lynch HT,Kosoko-Lasaki O,Leslie SW,Rendell M,Shaw T,Snyder C,D'Amico AV,Buxbaum S,Isaacs WB,Loeb S,Moul JW,Powell I

    更新日期:2016-06-01 00:00:00

  • A potentially functional polymorphism in the promoter region of miR-34b/c is associated with an increased risk for primary hepatocellular carcinoma.

    abstract::The miR-34 family members are direct transcriptional targets of tumor suppressor p53, and loss of miR-34 function can impair p53-mediated cell cycle arrest and apoptosis. A potentially functional SNP rs4938723 (T > C) was found in the promoter region of pri-miR-34b/c (423 bp from the transcription start site), located...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Xu Y,Liu L,Liu J,Zhang Y,Zhu J,Chen J,Liu S,Liu Z,Shi H,Shen H,Hu Z

    更新日期:2011-01-15 00:00:00

  • Human papillomavirus and cervical intraepithelial neoplasia grade II-III: a population-based case-control study.

    abstract::The association between certain human papillomaviruses (HPV) and cervical intraepithelial neoplasia (CIN) is well documented, but there is uncertainty about the strength of association and the role of co-factors is unclear. This population-based case-control study in Norwegian women 20-44 years of age included 103 cas...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Olsen AO,Gjøen K,Sauer T,Orstavik I,Naess O,Kierulf K,Sponland G,Magnus P

    更新日期:1995-05-04 00:00:00

  • Human melanoma cells can be killed in vitro by an immunotoxin specific for melanoma-associated antigen p97.

    abstract::Conjugates (immunotoxins) comprising ricin A-chain and monoclonal antibody 96.5, which is specific for human melanoma-associated antigen p97, inhibited protein synthesis and colony formation of cultured human melanoma cells that expressed more than 80,000 molecules of p97 per cell. Cells expressing fewer than 5,000 mo...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Casellas P,Brown JP,Gros O,Gros P,Hellström I,Jansen FK,Poncelet P,Roncucci R,Vidal H,Hellström KE

    更新日期:1982-10-15 00:00:00

  • No evidence for simian virus 40 DNA sequences in malignant non-Hodgkin lymphomas.

    abstract::DNA sequences coding for simian virus 40 (SV40) large T antigen have been detected at different frequencies in human non-Hodgkin's lymphomas (NHL) by PCR techniques as well as immunohistochemistry. A highly sensitive quantitative real-time PCR specific for a sequence of SV40 large T antigen was established to test whe...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Schüler F,Dölken SC,Hirt C,Dölken MT,Mentel R,Gürtler LG,Dölken G

    更新日期:2006-01-15 00:00:00

  • Role of the genetic background of rats in infection by HTLV-I and HTLV-II and in the development of associated diseases.

    abstract::Three aspects of the rat model of HTLV-I/II infection were investigated. (i) The efficacy of HTLV-I-transformed rat cell lines in infecting different strains of rats: WKY and Lewis HTLV-I-transformed cell lines were injected into adult WKY, Lewis and Brown Norway rats, representing syngeneic and allogeneic combination...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Kazanji M,Ibrahim F,Fiette L,Bomford R,De Thé G

    更新日期:1997-09-26 00:00:00

  • Organotropism of the lymphoproliferative disease virus (LPDV) of turkeys.

    abstract::Turkey poults were inoculated with lymphoproliferative disease virus (LPDV) of turkey, and the organotropism of the inoculated virus was determined from the kinetics of virus expression and tumor formation. Molecular hybridization experiments, conducted to determine the level of viral RNA expression in the various org...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Gazit A,Schwarzbard Z,Yaniv A,Ianconescu M,Perk K,Zimber A

    更新日期:1982-05-15 00:00:00

  • Biology of tumor cell invasion: interplay of cell adhesion and matrix degradation.

    abstract::Invasion of malignant cells requires altered cellular interaction with extracellular matrix. Integrin-type cell adhesion receptors play an important role in this process. Integrin-related cell biological phenomena explain cancer cell migration, and recent developments in the field have made it possible to propose that...

    journal_title:International journal of cancer

    pub_type: 杂志文章,评审


    authors: Heino J

    更新日期:1996-03-15 00:00:00

  • Mutation and expression of the p53 gene in malignant melanoma cell lines.

    abstract::Three monoclonal antibodies (MAbs) against p53 protein (PAb 24o, DO-I and PAb1801) were used to define the immunophenotype of 13 melanoma cell lines. Immunoreactions could be detected in 12 out of 13 cell lines by using the indirect immunofluorescence technique. In 7 of these the majority of cells displayed cytoplasmi...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Weiss J,Schwechheimer K,Cavenee WK,Herlyn M,Arden KC

    更新日期:1993-06-19 00:00:00

  • Differential antiproliferative actions of 2',5' oligo A trimer core and its cordycepin analogue on human tumor cells.

    abstract::The antiproliferative effect of 2',5' A3 core and 2',5'-3'dA3 (cordycepin trimer) core was measured in 8 human tumor cell lines. Cells were treated in a dose-response manner for 72 hr and the concentration of drug necessary to inhibit cell growth 50% (GI50) was determined. A wide range of sensitivities to these drugs ...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Hubbell HR,Pequignot EC,Willis DH,Lee C,Suhadolnik RJ

    更新日期:1985-09-15 00:00:00

  • Downregulation of SERPINB13 expression in head and neck squamous cell carcinomas associates with poor clinical outcome.

    abstract::Tumorigenesis of head and neck squamous cell carcinomas (HNSCC) is associated with various genetic changes such as loss of heterozygosity (LOH) on human chromosome 18q21. This chromosomal region maps a gene cluster coding for a family of intracellular serine protease inhibitors (serpins), including SERPINB13. As SERPI...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: de Koning PJ,Bovenschen N,Leusink FK,Broekhuizen R,Quadir R,van Gemert JT,Hordijk GJ,Chang WS,van der Tweel I,Tilanus MG,Kummer JA

    更新日期:2009-10-01 00:00:00

  • Bacterial surface display of endoglin by antigen 43 induces antitumor effectiveness via bypassing immunotolerance and inhibition of angiogenesis.

    abstract::Various angiogenesis-related self-molecules have been considered to be therapeutic targets. However, the direct use of self-molecules as vaccines is not recommended because of the inherent ability of the host to develop immune tolerance. Antigen 43 (Ag43) is a surface protein found in E. coli and contains an α and a β...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Huang FY,Li L,Liu Q,Li YN,Bai RZ,Huang YH,Zhao HG,Guo JL,Zhou SL,Wang H,Lin YY,Tan GH

    更新日期:2014-04-15 00:00:00

  • Chromosome-9 loss detected by fluorescence in situ hybridization in bladder cancer.

    abstract::A loss of chromosome-9 material is one of the most frequent genomic aberrations known in bladder cancer. In order to better understand the role of chromosome-9 losses in bladder cancer, 125 formalin-fixed and 37 unfixed bladder tumors were examined using fluorescence in situ hybridization (FISH). A repetitive probe fo...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Sauter G,Moch H,Carroll P,Kerschmann R,Mihatsch MJ,Waldman FM

    更新日期:1995-04-21 00:00:00

  • Down-regulation of protein and mRNA expression for transforming growth factor-beta (TGF-beta1) type I and type II receptors in human prostate cancer.

    abstract::Transforming growth factor-beta (TGF-beta1) is a potent negative regulator of cell growth that transduces signals through interactions with type I and II receptors. Abnormal expression and mutational alterations of these receptors have been observed in several human malignancies. In this study, we investigated the exp...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Guo Y,Jacobs SC,Kyprianou N

    更新日期:1997-05-16 00:00:00

  • Phenotypes correlating to metastatic properties of pancreas adenocarcinoma in vivo: the importance of surface sialyl Lewis(a) antigen.

    abstract::Metastasis to the liver often occurs in patients during the natural course of pancreatic cancer. Using carcinoma cell lines established from 9 such patients, we examined phenotypes of cell lines to search for correlations with their potential to metastasize to the liver. Anti-asialo GMI-treated nude mice were used. PC...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Kishimoto T,Ishikura H,Kimura C,Takahashi T,Kato H,Yoshiki T

    更新日期:1996-08-22 00:00:00

  • Clinicopathologic significance of urokinase receptor- and MMP-9-positive stromal cells in human colorectal cancer: functional multiplicity of matrix degradation on hematogenous metastasis.

    abstract::Our previous clinicopathologic study revealed an inverse association of liver metastasis of colorectal cancer and stromal expression of matrix metalloproteinase-9 (MMP-9) or urokinase receptor (uPAR). This suggests that host cells, particularly macrophages, expressing matrix-degrading enzymes/factors could be protecti...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Saito K,Takeha S,Shiba K,Matsuno S,Sorsa T,Nagura H,Ohtani H

    更新日期:2000-04-01 00:00:00

  • IGF2R polymorphisms and risk of esophageal and gastric adenocarcinomas.

    abstract::The mannose-6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) encodes a protein that plays a critical role in tumor suppression, in part by modulating bioavailability of a potent mitogen, insulin-like growth factor-2 (IGF2). We tested the hypothesis that the common nonsynonymous genetic variants in M6P/IGF...

    journal_title:International journal of cancer

    pub_type: 杂志文章,多中心研究


    authors: Hoyo C,Schildkraut JM,Murphy SK,Chow WH,Vaughan TL,Risch H,Marks JR,Jirtle RL,Calingaert B,Mayne S,Fraumeni J Jr,Gammon MD

    更新日期:2009-12-01 00:00:00

  • Relationship of circulating tumor cells and Epstein-Barr virus DNA to progression-free survival and overall survival in metastatic nasopharyngeal carcinoma patients.

    abstract::We analyzed the number of circulating tumor cells (CTCs) and Epstein-Barr virus DNA (EBV DNA) for diagnosis, monitoring and prognosis of patients with metastatic nasopharyngeal carcinoma (mNPC). The levels of CTCs and EBV DNA were measured at baseline and after first-line chemotherapy in 148 mNPC patients prospectivel...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: You R,Liu YP,Lin M,Huang PY,Tang LQ,Zhang YN,Pan Y,Liu WL,Guo WB,Zou X,Zhao KM,Kang T,Liu LZ,Lin AH,Hong MH,Mai HQ,Zeng MS,Chen MY

    更新日期:2019-11-15 00:00:00

  • Evaluation of circulating EBV microRNA BART2-5p in facilitating early detection and screening of nasopharyngeal carcinoma.

    abstract::Nasopharyngeal carcinoma is an Epstein-Barr Virus (EBV) associated malignancy which is highly prevalent in Southeast Asia. EBV-related antibodies have been widely used as screening markers for early nasopharyngeal carcinoma (NPC) detection. However, due to its low positive predictive rate, it is essential to develop n...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Jiang C,Chen J,Xie S,Zhang L,Xiang Y,Lung M,Kam NW,Kwong DL,Cao S,Guan XY

    更新日期:2018-12-15 00:00:00

  • Progenitor and pre-B lymphocytes transformed by Epstein-Barr virus.

    abstract::By rosetting with SRBC coupled to rabbit-anti-human IgM, the surface IgM-negative cells of human fetal bone marrow were enriched, and subsequently infected and transformed by Epstein-Barr virus (EBV). Single clones of the transformed cells were obtained. Ninety percent of the resulting cell clones were surface-immunog...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Ernberg I,Falk K,Hansson M

    更新日期:1987-02-15 00:00:00

  • Genetic variants in TNF-α promoter are predictors of recurrence in patients with squamous cell carcinoma of oropharynx after definitive radiotherapy.

    abstract::The promoter variants of TNF-α, a major regulator of immune and inflammation responses, have been implicated in cancer development and prognosis. Thus, we investigated associations between four TNF-α promoter variants and risk of recurrence of squamous cell carcinoma of the oropharynx (SCCOP). We evaluated association...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Zhang C,Sturgis EM,Zheng H,Song X,Wei P,Jin L,Chao L,Wei Q,Li G

    更新日期:2014-04-15 00:00:00

  • Karyotype evolution in a transformed rat cerebral endothelial cell line.

    abstract::Primary cultures of rat microvascular endothelial cells were transformed, in vitro, by exposure to Rous sarcoma virus. Transformed cells were followed and evaluated cytogenetically through numerous passages. Highly specific karyotypic changes in karyotype (both structural and numerical) were documented. These changes ...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Tyrkus M,Diglio CA,Gohle N

    更新日期:1983-10-15 00:00:00

  • HER3 is required for the maintenance of neuregulin-dependent and -independent attributes of malignant progression in prostate cancer cells.

    abstract::HER3 (ERBB3) is a catalytically inactive pseudokinase of the HER receptor tyrosine kinase family, frequently overexpressed in prostate and other cancers. Aberrant expression and mutations of 2 other members of the family, EGFR and HER2, are key carcinogenic events in several types of tumors, and both are well- validat...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Soler M,Mancini F,Meca-Cortés O,Sánchez-Cid L,Rubio N,López-Fernández S,Lozano JJ,Blanco J,Fernández PL,Thomson TM

    更新日期:2009-12-01 00:00:00

  • Folate intake and colorectal cancer risk: a meta-analytical approach.

    abstract::Adequate consumption of folate may reduce the risk of colorectal cancer. We performed a meta-analysis of 7 cohort and 9 case-control studies that examined the association between folate consumption and colorectal cancer risk. In cohort studies, the association between folate consumption and colorectal cancer risk was ...

    journal_title:International journal of cancer

    pub_type: 杂志文章,meta分析


    authors: Sanjoaquin MA,Allen N,Couto E,Roddam AW,Key TJ

    更新日期:2005-02-20 00:00:00

  • Cytogenetic abnormalities in benign lymphoid hyperplasia: a dual-parameter study using chromosome analysis and flow cytometry.

    abstract::This is a prospective study of lymphoid tissue showing benign reactive hyperplasia (18 lymph nodes and 2 tonsils), using cytogenetic analysis of cells stimulated with T- or B-cell mitogens. The reason for this study was the detection of an abnormal chromosomal population in cells from an enlarged lymph node excised fr...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Grace J,Hall BE,Lew M,Singh S,Pittman S,Palmer AA,Zbroja R,Wass J,Vincent PC

    更新日期:1989-12-15 00:00:00

  • Promoting effects of monomethylarsonic acid, dimethylarsinic acid and trimethylarsine oxide on induction of rat liver preneoplastic glutathione S-transferase placental form positive foci: a possible reactive oxygen species mechanism.

    abstract::Dimethylarsinic acid (DMA) is a major metabolite of inorganic arsenicals, which are epidemiologically significant chemicals in relation to liver cancer in mammals. The present study was conducted to determine the promoting effects of organic arsenicals related to DMA [monomethylarsonic acid (MMA) and trimethylarsine o...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Nishikawa T,Wanibuchi H,Ogawa M,Kinoshita A,Morimura K,Hiroi T,Funae Y,Kishida H,Nakae D,Fukushima S

    更新日期:2002-07-10 00:00:00

  • Presentation of native TROP-2 tumor antigens to human cytotoxic T lymphocytes by engineered antigen-presenting cells.

    abstract::Professional antigen-presenting cells (APC), e.g. dendritic cells, express immuno-proteasome components and process proteins for MHC presentation differently from non-immune cells. Thus, they induce reactivities against sets of peptides that do not overlap with those generated by non-professional APC, i.e., tumor cell...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Mangino G,Grazia Capri M,Barnaba V,Alberti S

    更新日期:2002-10-01 00:00:00