ETS1 is coexpressed with ZEB2 and mediates ZEB2-induced epithelial-mesenchymal transition in human tumors.

Abstract:

:Epithelial-mesenchymal transition (EMT) is an embryonic program that is reactivated in cancer and regulates the invasion and metastasis of tumor cells. Zinc finger E-box binding homeobox 2 (ZEB2) induces EMT by upregulating matrix metalloproteinases (MMP), yet MMP genes lack ZEB2 binding motif in their promoters. Recently, expression of MMPs was associated to the activation of ETS1 transcription factor; however, a link between ZEB2 and ETS proto-oncogene 1, transcription factor (ETS1) remains to be elucidated. Hence, we investigated the transcriptional regulation of ETS1 by ZEB2 after our initial observation that ZEB2 and ETS1 are coexpressed in hepatocellular carcinoma cells (HCCs). Chromatin immunoprecipitation and luciferase reporter assays clearly showed that ZEB2 binds to E-box sequences on the promoter of ETS1. Elevated expression of ETS1 was found in DLD-ZEB2 and A431-ZEB2 inducible systems, and knockdown of ZEB2 caused an explicit downregulation of ETS1 in shZEB2-SNU398 and shZEB2-SK-HEP-1 cells. Repression of ETS1 expression in ZEB2-induced conditions substantially impaired the migration and invasive capacities of DLD1 cells. Mechanistically, knockdown of ETS1 in ZEB2-expressing cells resulted in the downregulation of established ZEB2 targets TWIST and MMP9. Correlation analyses in HCC lines, cancer complementary DNA arrays, and The Cancer Genome Atlas RNA-sequencing data set revealed that ZEB2 and ETS1 are coexpressed, and their expressions in human tumors show a highly significant positive correlation. Our results demonstrated that ZEB2 acts as an upstream regulator of ETS1 and, in turn, ETS1 maintains ZEB2-induced EMT. These findings add another level of complexity to the understanding of ZEB2 in the invasion and metastasis of cancer cells, and put ZEB2/ETS1 axis as a novel therapeutic target in human malignancies.

journal_name

Mol Carcinog

journal_title

Molecular carcinogenesis

authors

Yalim-Camci I,Balcik-Ercin P,Cetin M,Odabas G,Tokay N,Sayan AE,Yagci T

doi

10.1002/mc.22994

subject

Has Abstract

pub_date

2019-06-01 00:00:00

pages

1068-1081

issue

6

eissn

0899-1987

issn

1098-2744

journal_volume

58

pub_type

杂志文章
  • Modulation of the oncogenic potential of beta-catenin by the subcellular distribution of plakoglobin.

    abstract::Plakoglobin (Pg) and beta-catenin are homologous proteins that function in cell-cell adhesion and signaling. The cadherin-associated form of these proteins mediates adhesion, whereas the cytosolic/nuclear form has a signaling role. Despite their interactions with common cellular partners, beta-catenin has a well-docum...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20310

    authors: Li L,Chapman K,Hu X,Wong A,Pasdar M

    更新日期:2007-10-01 00:00:00

  • Inhibition of proliferation and expression of T1 and cyclin D1 genes by thyroid hormone in mammary epithelial cells.

    abstract::The relationship between thyroid hormone (triiodothyronine, T(3)) and breast cancer is unclear. We studied the effect of the c-erbA/TR alpha proto-oncogene encoding a functional T(3) receptor (TR alpha 1), of its ligand T(3), and of its retroviral, mutated counterpart, the v-erbA oncogene, on the proliferation capacit...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.10046

    authors: González-Sancho JM,Figueroa A,López-Barahona M,López E,Beug H,Muñoz A

    更新日期:2002-05-01 00:00:00

  • The infant mouse as a in vivo model for the detection and study of DNA damage-induced changes in the liver.

    abstract::The present work describes the use of the infant (4-wk-old) mouse as an animal model for the study of DNA damage-induced G(1) checkpoint response, changes in p53 protein levels, and multiple gene expression changes after DNA damage has been induced in the liver. Hepatocytes in the infant B6C3F1 mouse had a proliferati...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20017

    authors: Reynolds R,Witherspoon S,Fox T

    更新日期:2004-05-01 00:00:00

  • Molecular evidence supporting the precursor nature of atypical adenomatous hyperplasia of the prostate.

    abstract::Atypical adenomatous hyperplasia (AAH) of the prostate is characterized by lobular proliferation of closely packed small acini. It is hypothesized that AAH is a precursor lesion for low-grade prostate cancer arising from the transition zone. Telomere dysfunction is common during malignant transformation of epithelia. ...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.23009

    authors: Cheng L,Montironi R,Davidson DD,Wang M,Lopez-Beltran A,Zhang S

    更新日期:2019-07-01 00:00:00

  • Longitudinal change of metabolite profile and its relation to multiple risk factors for the risk of developing hepatitis B-related hepatocellular carcinoma.

    abstract::Despite considerable knowledge of viral pathogenesis, the pathophysiological changes related to the multifactorial, multistep process of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) development remains unclear. Longitudinal metabolomics study can reveal biological process for disease progression. We ...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.23255

    authors: Huang BY,Tsai MR,Hsu JK,Lin CY,Lin CL,Hu JT,Huang YW,Liu CJ,Wu WJ,Wu CF,Sung FY,Chen PJ,Liang HJ,Lin SM,Yu MW

    更新日期:2020-11-01 00:00:00

  • Osteoblasts-derived TGF-beta1 enhance motility and integrin upregulation through Akt, ERK, and NF-kappaB-dependent pathway in human breast cancer cells.

    abstract::Bone metastases are common complications of breast cancer. Integrins are the major adhesive molecules in mammalian cells. Here we found that osteoblast conditioned medium (OBCM) increased the migration and cell surface expression of beta1 or beta3 integrin in human breast cancer cells (MDA-MB-231 cells). beta1 or beta...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20411

    authors: Wei YY,Chen YJ,Hsiao YC,Huang YC,Lai TH,Tang CH

    更新日期:2008-07-01 00:00:00

  • A comparative analysis of allelic imbalance events in chemically induced rat mammary, colon, and bladder tumors.

    abstract::In this paper, patterns of allelic imbalances (Als) in chemically induced rat mammary, colon, and bladder tumors from (Wistar Furth x Fischer 344)F1 rats are described and compared. Male F1 rats were administered azoxymethane (AOM), and colon tumors were collected at 58 wk after treatment. Female F1 rats were given ei...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/(sici)1098-2744(199901)24:1<47::aid-mc7>3.

    authors: Haag JD,Brasic GM,Shepel LA,Newton MA,Grubbs CJ,Lubet RA,Kelloff GJ,Gould MN

    更新日期:1999-01-01 00:00:00

  • Tumorigenic study on hepatocytes coexpressing SV40 with Ras.

    abstract::A model of neoplastic transformation by the combination of SV40 large T antigen (LT), SV40 small T antigen (ST), oncogenic Ras, and human telomerase reverse trasncriptase subunit (hTERT) has become established and replicated in primary human fibroblasts, however, there is no report on human hepatocytes. Here we use ce...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20137

    authors: Sun B,Chen M,Hawks C,Hornsby PJ,Wang X

    更新日期:2006-04-01 00:00:00

  • SERPINB2 down-regulation contributes to chemoresistance in head and neck cancer.

    abstract::Resistance to cisplatin-based chemotherapy is responsible for the majority of deaths from head and neck squamous cell carcinoma (HNSCC). In this study, using genome-wide gene expression analysis to investigate potential molecular mediators of HNSCC chemoresistance, we identified SERPINB2, a known inhibitor of extracel...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22033

    authors: Huang Z,Li H,Huang Q,Chen D,Han J,Wang L,Pan C,Chen W,House MG,Nephew KP,Guo Z

    更新日期:2014-10-01 00:00:00

  • Upregulation of the long non-coding RNA HOTAIR promotes esophageal squamous cell carcinoma metastasis and poor prognosis.

    abstract::Recent studies of the individual functionalities of long non-coding RNAs (lncRNAs) in the development and progression of cancer have suggested that HOX transcript antisense RNA (HOTAIR) is capable of reprogramming chromatin organization and promoting cancer cell metastasis. In order to ascertain the expression pattern...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.21944

    authors: Chen FJ,Sun M,Li SQ,Wu QQ,Ji L,Liu ZL,Zhou GZ,Cao G,Jin L,Xie HW,Wang CM,Lv J,De W,Wu M,Cao XF

    更新日期:2013-11-01 00:00:00

  • Infrequent loss of heterozygosity and mutation of the p53 gene in immortal and transformed mouse embryo fibroblasts.

    abstract::Some of the progeny of isolated mouse embryo fibroblasts acquire the ability to grow indefinitely during cultivation, presumably through some mutational events. The relevance of p53 mutations and loss of heterozygosity to the mechanism of such immortal growth capability remains controversial. Since four bases in intro...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.2940100109

    authors: Tokumitsu M,Kadohama T,Ogawa K

    更新日期:1994-05-01 00:00:00

  • The enhancing effects of obesity on mammary tumor growth and Akt/mTOR pathway activation persist after weight loss and are reversed by RAD001.

    abstract::The prevalence of obesity, an established risk and progression factor for postmenopausal breast cancer, remains high in US women. Activation of Akt/mammalian target of rapamycin (mTOR) signaling plays a key role in the obesity-breast cancer link. However, the impact of weight normalization in obese postmenopausal wome...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.21878

    authors: De Angel RE,Conti CJ,Wheatley KE,Brenner AJ,Otto G,Degraffenried LA,Hursting SD

    更新日期:2013-06-01 00:00:00

  • Twist1 regulates keratinocyte proliferation and skin tumor promotion.

    abstract::In the present study, we evaluated the effect of deleting Twist1 on keratinocyte proliferation and on skin tumor development using the two-stage chemical carcinogenesis model. BK5.Cre × Twist1(flox/flox) mice, which have a keratinocyte-specific Twist1 knockout (Twist1 KO), developed significantly reduced numbers of pa...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22335

    authors: Srivastava J,Rho O,Youssef RM,DiGiovanni J

    更新日期:2016-05-01 00:00:00

  • Grb2-associated binder 1 (Gab1) genetic polymorphism, Helicobacter pylori infection, and chronic atrophic gastritis among older adults from Germany.

    abstract::Grb2-associated binder 1 (Gab1) plays an important role in the regulation of cell growth and transformation. A single nucleotide polymorphism (SNP) (rs3805246) in the Gab1 gene has been suggested to be related to the risk of Helicobacter pylori infection and chronic atrophic gastritis (CAG) in a study from Japan. We a...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20662

    authors: Gao L,Weck MN,Nieters A,Brenner H

    更新日期:2010-10-01 00:00:00

  • Oncogene RNA helicase DDX6 promotes the process of c-Myc expression in gastric cancer cells.

    abstract::Human DEAD-box RNA helicase gene DDX6 was cloned from B-cell lymphoma cell line RC-K8. Previously, we reported that DDX6 acts as oncogene in several cancers such as colorectal cancer and hepatocellular carcinoma. However, the detailed mechanism of DDX6 action in carcinogenesis is largely unknown. In this study, we exa...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22781

    authors: Taniguchi K,Iwatsuki A,Sugito N,Shinohara H,Kuranaga Y,Oshikawa Y,Tajirika T,Futamura M,Yoshida K,Uchiyama K,Akao Y

    更新日期:2018-05-01 00:00:00

  • Chromium IV exposure, via Src/Ras signaling, promotes cell transformation.

    abstract::Hexavalent chromium [Cr(VI)] is a well-known environment carcinogen. The exposure of Cr(VI) through contaminated soil, air particles, and drinking water is a strong concern for the public health worldwide. While many studies have been done, it remains unclear which intracellular molecules transduce Cr(VI)-mediated car...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22639

    authors: Ganapathy S,Li P,Lafontant J,Xiong R,Yu T,Zhang G,Chen C

    更新日期:2017-07-01 00:00:00

  • The role of transforming growth factor-beta in immune suppression and chronic inflammation of squamous cell carcinomas.

    abstract::Despite a decline in the incidence of squamous cell carcinomas (SCCs) over the past 20 years, their survival rate has remained nearly the same, indicating that treatment options have not improved relative to other cancer types. Immunotherapies have a high potential for a sustained effect in SCC patients, but their res...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章,评审

    doi:10.1002/mc.23196

    authors: Strait AA,Wang XJ

    更新日期:2020-07-01 00:00:00

  • Isosilybin A induces apoptosis in human prostate cancer cells via targeting Akt, NF-κB, and androgen receptor signaling.

    abstract::Prostate cancer (PCA) is the second most malignancy in American men. Advanced stage PCA cells possess unlimited replication potential as well as resistance to apoptosis. Therefore, targeting survival mechanisms and activating apoptotic machinery in PCA cells using nontoxic phytochemicals is suggested as an attractive ...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20670

    authors: Deep G,Gangar SC,Oberlies NH,Kroll DJ,Agarwal R

    更新日期:2010-10-01 00:00:00

  • A p53 mutation in exon 5 associated with adenovirus transformation.

    abstract::The adenovirus type 5 (Ad5) 55-kDa E1B oncoprotein has been shown to form complexes with the p53 tumor suppressor protein. These complexes are thought to interfere with normal p53 activity and may be responsible for the paucity of p53 mutations in cells transformed by these viruses. This report describes an example of...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.2940120102

    authors: Eyler YL,Siwarski DF,Huppi KE,Lewis AM Jr

    更新日期:1995-01-01 00:00:00

  • Diallyl trisulfides, a natural histone deacetylase inhibitor, attenuate HIF-1α synthesis, and decreases breast cancer metastasis.

    abstract::Intratumoral hypoxia promotes the distant metastasis of cancer subclones. The clinical expression level of hypoxia-inducible factor-1α (HIF-1α) reflects the prognosis of a variety of cancers, especially breast cancer. Histone deacetylase (HDAC) inhibitors can target HIF-1α protein due to von Hippel-Lindau (VHL) protei...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22686

    authors: Wei Z,Shan Y,Tao L,Liu Y,Zhu Z,Liu Z,Wu Y,Chen W,Wang A,Lu Y

    更新日期:2017-10-01 00:00:00

  • Protection against oxidative DNA damage and stress in human prostate by glutathione S-transferase P1.

    abstract::The pi-class glutathione S-transferase (GSTP1) actively protect cells from carcinogens and electrophilic compounds. Loss of GSTP1 expression via promoter hypermethylation is the most common epigenetic alteration observed in human prostate cancer. Silencing of GSTP1 can increase generation of reactive oxygen species (R...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.21939

    authors: Kanwal R,Pandey M,Bhaskaran N,Maclennan GT,Fu P,Ponsky LE,Gupta S

    更新日期:2014-01-01 00:00:00

  • Matrix metalloproteinase3 gene promoter polymorphisms and their haplotypes are associated with gastric cancer risk in eastern Indian population.

    abstract::Single nucleotide polymorphisms (SNPs) of matrix metalloproteinase3 (MMP3) promoter in the development and progression of gastric cancer of whole stomach has never been investigated in any population. We conducted a hospital-based case-control study to explore the MMP3 SNPs and their haplotypes with the risk of gastri...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.21837

    authors: Dey S,Stalin S,Gupta A,Saha D,Kesh K,Swarnakar S

    更新日期:2012-10-01 00:00:00

  • Arachidonoyl ethanolamide (AEA)-induced apoptosis is mediated by J-series prostaglandins and is enhanced by fatty acid amide hydrolase (FAAH) blockade.

    abstract::The endocannabinoid arachidonoyl ethanolamide (AEA) is a potent inducer of tumor cell apoptosis however its mechanism of cytotoxicity is unclear. A previous report from our laboratory showed that AEA induced cell death in a cyclooxygenase-2 (COX-2)-dependent manner and in this report our data indicate that AEA-induced...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20770

    authors: Kuc C,Jenkins A,Van Dross RT

    更新日期:2012-02-01 00:00:00

  • Mutational specificity of 2-amino-3-methylimidazo-[4,5-f]quinoline in the hprt locus of CHO-K1 cells.

    abstract::2-Amino-3-methylimidazo[4,5-f]quinoline (IQ), a food carcinogen formed in cooked meats, can induce gene mutation at the hprt locus of CHO-K1 cells in the presence of hepatic S9 mix. To elucidate the molecular nature of IQ-induced mutation, we characterized the entire coding region of the hypoxanthine phosphoribosyl-tr...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.2940130209

    authors: Lee H,Shih MK

    更新日期:1995-06-01 00:00:00

  • Homozygous K5Cre transgenic mice have wavy hair and accelerated malignant progression in a murine model of skin carcinogenesis.

    abstract::Mice with conditional gene deletions have been extremely valuable in allowing investigators to study the genes of interest in a tissue-specific manner. The Cre-loxP recombination system provides a powerful tool to produce targeted rearrangements of particular genes. The keratin 5-Cre recombinase (K5Cre) transgenic mou...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20192

    authors: Chan EL,Peace BE,Toney K,Kader SA,Pathrose P,Collins MH,Waltz SE

    更新日期:2007-01-01 00:00:00

  • A Tcf4-GFP reporter mouse model for monitoring effects of Apc mutations during intestinal tumorigenesis.

    abstract::Apc mutations cause intestinal tumorigenesis through Tcf4 activation. However, direct techniques for studying Tcf4 activation in vivo are limited. Here, we describe the development of a Tcf4-GFP reporter mouse model for directly studying Tcf4 activation. We first developed a GFP reporter construct (Tcf4-GFP) and trans...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20526

    authors: Boman B,Kopelovich L,Siracusa LD,Zhang T,Henderson K,Cofer Z,Buchberg AM,Fields JZ,Otevrel T

    更新日期:2009-09-01 00:00:00

  • Stromal contributions to the carcinogenic process.

    abstract::Tumor-associated stromal cells are dynamic characters that endorse the carcinogenic process in a multitude of ways. The tumor microenvironment plays a crucial role throughout the tumor progression, which includes initiation, growth, invasion, and metastasis. The tumor microenvironment consists of cellular and non-cell...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章,评审

    doi:10.1002/mc.22583

    authors: Spaw M,Anant S,Thomas SM

    更新日期:2017-04-01 00:00:00

  • Melatonin modulated autophagy and Nrf2 signaling pathways in mice with colitis-associated colon carcinogenesis.

    abstract:UNLABELLED:Colon carcinogenesis is long known to be associated with ulcerative colitis (UC), a chronic gastrointestinal disorder. Various pre-clinical and clinical studies have shown that melatonin (MEL) has beneficial effects in cancer. However, elucidation of the detailed molecular mechanisms involved in MEL-mediated...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22274

    authors: Trivedi PP,Jena GB,Tikoo KB,Kumar V

    更新日期:2016-03-01 00:00:00

  • Kaempferol suppresses bladder cancer tumor growth by inhibiting cell proliferation and inducing apoptosis.

    abstract::The effects of the flavonoid compound, kaempferol, which is an inhibitor of cancer cell proliferation and an inducer of cell apoptosis have been shown in various cancers, including lung, pancreatic, and ovarian, but its effect has never been studied in bladder cancer. Here, we investigated the effects of kaempferol on...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22154

    authors: Dang Q,Song W,Xu D,Ma Y,Li F,Zeng J,Zhu G,Wang X,Chang LS,He D,Li L

    更新日期:2015-09-01 00:00:00

  • Harnessing the gatekeepers of glucocorticoids for chemoprevention of non-melanoma skin cancer.

    abstract::Despite effective surgical methods for non-melanoma skin cancer (NMSC), patients suffer from tissue damage, scarring, or even disfigurement; thus, there is a need for chemopreventive approaches. Because of the complex interplay between glucocorticoids (GCs), inflammation, and cancer, we sought to determine the role of...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22912

    authors: Mancha-Ramirez AM,Yang X,Liang H,Junco J,Lee KP,Bovio SF,Espinoza M,Wool J,Slaga A,Glade DC,Hanes M,Malik G,Kim DJ,DiGiovanni J,Slaga TJ

    更新日期:2019-01-01 00:00:00