LncAPC drives Wnt/β-catenin activation and liver TIC self-renewal through EZH2 mediated APC transcriptional inhibition.

Abstract:

:Liver tumor initiating cells (TICs), a small subset cells in tumor bulk, are responsible for liver tumor initiation, metastasis, and relapse. However, the regulatory mechanism of liver TICs remains largely unknown. Here we found a long noncoding RNA lncAPC, locating near from APC locus, was highly expressed in liver cancer and liver TICs. LncAPC was required for liver TIC self-renewal. Silencing and overexpressing lncAPC showed impaired and enhanced sphere formation capacity of liver TICs, respectively. By recruiting EZH2 to APC promoter, LncAPC inhibits APC transcription and thus drives the activation of Wnt/β-catenin signaling. Attenuate binding between EZH2 and APC promoter was observed upon lncAPC knockdown. What is more, lncAPC-EZH2-APC axis can be targeted to eliminate liver TICs. Altogether, LncAPC promotes liver TIC self-renewal through EZH2-dependent APC transcriptional inhibition.

journal_name

Mol Carcinog

journal_title

Molecular carcinogenesis

authors

Fu X,Lin J,Qin F,Yang Z,Ding Y,Zhang Y,Han L,Zhu X,Zhang Q

doi

10.1002/mc.22764

subject

Has Abstract

pub_date

2018-03-01 00:00:00

pages

408-418

issue

3

eissn

0899-1987

issn

1098-2744

journal_volume

57

pub_type

杂志文章
  • 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. Rece...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22994

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

    更新日期:2019-06-01 00:00:00

  • A Zbtb7a proto-oncogene as a novel target for miR-125a.

    abstract::In our previous study, we showed that miR-125a directly targeted a WT1 oncogene, which was overexpressed in leukemia and various kinds of solid tumors including lung, breast, gastric, and colon cancers, and brain tumors and was deeply involved in leukemogenesis and tumorigenesis and that miR-125a knockout mice overexp...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22446

    authors: Hojo N,Tatsumi N,Moriguchi N,Matsumura A,Morimoto S,Nakata J,Fujiki F,Nishida S,Nakajima H,Tsuboi A,Oka Y,Hosen N,Hayashi S,Sugiyama H,Oji Y

    更新日期:2016-12-01 00:00:00

  • Apurinic/apyrimidinic endonuclease 1 (APE1/Ref-1) overexpression is an independent prognostic marker in prostate cancer without TMPRSS2:ERG fusion.

    abstract::Polymorphisms of the base excision repair gene APE1 may be associated with an increased risk for developing prostate cancer. In other cancer types, altered APE1 protein expression is a candidate prognostic marker. Using immunohistochemistry, we thus analyzed APE1 expression in 9763 prostate cancers in a tissue microar...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22670

    authors: Juhnke M,Heumann A,Chirico V,Höflmayer D,Menz A,Hinsch A,Hube-Magg C,Kluth M,Lang DS,Möller-Koop C,Sauter G,Simon R,Beyer B,Pompe R,Thederan I,Schlomm T,Luebke AM

    更新日期:2017-09-01 00:00:00

  • Accumulation of aberrant Y chromosomes in gamma-ray-induced thymic lymphomas lacking p53.

    abstract::Male F(1) hybrids between MSM mice carrying a deficient p53 allele and BALB/c mice were irradiated with gamma-rays, and 80 thymic lymphomas were obtained, 46 of which developed in mice carrying the deficient p53 allele. Because the Y chromosome contributes little to cellular function, the stability of the Y chromosome...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:

    authors: Chou D,Matsuki J,Saitou Y,Kosugi SI,Shinbo T,Gejyo F,Niwa O,Kominami R

    更新日期:1999-11-01 00:00:00

  • Characterization of the basal and carcinogen regulatory elements of the rat mdr1b promoter.

    abstract::In this report we characterized the transcriptional regulation of the rat mdr1b gene by xenobiotics. The expression of this gene was increased in primary rat hepatocytes and in the H4-II-E hepatoma cell line by exposure to carcinogens such as aflatoxin B1, N-acetoxy-2-acetylaminofluorene, and methyl methanesulfonate. ...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.2940130109

    authors: Silverman JA,Hill BA

    更新日期:1995-05-01 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

  • Mutational specificities of environmental carcinogens in the lacl gene of Escherichia coli. III: The cyclic nitrosamine N-nitrosopyrrolidine is a complex mutagen.

    abstract::The mutational specificity of the cyclic nitrosamine N-nitrosopyrrolidine (NPYR) was determined through the DNA sequence characterization of 33 lacl-d mutations of Escherichia coli. Base substitution was the predominant class of mutation induced (91%). The majority of these (64%) occurred at GC base pairs, in accordan...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.2940030304

    authors: Zielenska M,Ahmed A,Glickman BW

    更新日期:1990-01-01 00:00:00

  • Phenotypic characteristics of mouse lung adenoma induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.

    abstract::The expression profile of adenoma induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in A/J mice was compared with that of normal lung tissue by suppression subtractive hybridization (SSH). The mRNAs of surfactant-associated protein A (SP-A) and lysozyme showed characteristically higher transcription in t...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20070

    authors: Okubo C,Morishita Y,Minami Y,Ishiyama T,Kano J,Iijima T,Noguchi M

    更新日期:2005-02-01 00:00:00

  • 2-methoxyestradiol blocks cell-cycle progression at G(2)/M phase and inhibits growth of human prostate cancer cells.

    abstract::2-Methoxyestradiol (2-ME), an endogenous metabolite of 17beta-estradiol, is present in human blood and urine. Here we show for the first time that 2-ME significantly inhibited the growth of normal prostate epithelial cells and androgen-dependent LNCaP and androgen-independent DU145 prostate cancer cells. This growth i...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.1046

    authors: Kumar AP,Garcia GE,Slaga TJ

    更新日期:2001-07-01 00:00:00

  • Inhibition of constitutively activated phosphoinositide 3-kinase/AKT pathway enhances antitumor activity of chemotherapeutic agents in breast cancer susceptibility gene 1-defective breast cancer cells.

    abstract::Loss or decrease of wild type BRCA1 function, by either mutation or reduced expression, has a role in hereditary and sporadic human breast and ovarian cancers. We report here that the PI3K/AKT pathway is constitutively active in BRCA1-defective human breast cancer cells. Levels of phospho-AKT are sustained even after ...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.21905

    authors: Yi YW,Kang HJ,Kim HJ,Hwang JS,Wang A,Bae I

    更新日期:2013-09-01 00:00:00

  • Targeting c-MET by LY2801653 for treatment of cholangiocarcinoma.

    abstract::Palliative treatment options for human cholangiocarcinoma (CCC) are quite limited and new therapeutic strategies are of utmost need. c-MET has been shown to be deregulated in many cancers, but the role of c-MET in the carcinogenesis of CCC remains unclear. The main purpose of this study is to evaluate the expression a...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22449

    authors: Barat S,Bozko P,Chen X,Scholta T,Hanert F,Götze J,Malek NP,Wilkens L,Plentz RR

    更新日期:2016-12-01 00:00:00

  • Apigenin, a chemopreventive bioflavonoid, induces AMP-activated protein kinase activation in human keratinocytes.

    abstract::AMP-activated protein kinase (AMPK) is a cellular energy sensor that is conserved in eukaryotes. Although AMPK is traditionally thought to play a major role in the regulation of cellular lipid and protein metabolism, recent discoveries reveal that AMPK inhibits mammalian target of rapamycin (mTOR) signaling and connec...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20793

    authors: Tong X,Smith KA,Pelling JC

    更新日期:2012-03-01 00:00:00

  • Grape seed extract and resveratrol prevent 4-nitroquinoline 1-oxide induced oral tumorigenesis in mice by modulating AMPK activation and associated biological responses.

    abstract::Preventive measures against oral carcinogenesis are urgently warranted to lower the high morbidity and mortality associated with this malignancy worldwide. Here, we investigated the chemopreventive efficacy of grape seed extract (GSE) and resveratrol (Res) in 4-nitroquinoline-1-oxide (4NQO)-induced tongue tumorigenesi...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22099

    authors: Shrotriya S,Tyagi A,Deep G,Orlicky DJ,Wisell J,Wang XJ,Sclafani RA,Agarwal R,Agarwal C

    更新日期:2015-04-01 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

  • 2-Hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine induction of recombinational mutations in mammalian cell lines as detected by DNA fingerprinting.

    abstract::2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abundant mutagenic heterocyclic amine in cooked foods. Two mouse tumor cell lines, BMT11 and FM3A, were exposed to its proximate form, 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (N-OH-PhIP). Fifty-six subclones of BMT11 and 39 subclones of ...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.2940090203

    authors: Kitazawa T,Kominami R,Tanaka R,Wakabayashi K,Nagao M

    更新日期:1994-02-01 00:00:00

  • MDM2 promoter polymorphism and p53 codon 72 polymorphism in chronic myeloid leukemia: the association between MDM2 promoter genotype and disease susceptibility, age of onset, and blast-free survival in chronic phase patients receiving imatinib.

    abstract::The genetic or functional inactivation of the p53 pathway plays an important role with regards to disease progression from the chronic phase (CP) to blast phase (BP) and imatinib treatment response in chronic myeloid leukemia (CML). Two functional single nucleotide polymorphisms (SNPs), p53 R72P and MDM2 SNP309, are a...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22061

    authors: Liu YC,Hsiao HH,Yang WC,Liu TC,Chang CS,Yang MY,Lin PM,Hsu JF,Lee CP,Lin SF

    更新日期:2014-12-01 00:00:00

  • Increased expression of and sensitivity to transforming growth factor-alpha: a promotive role during rat liver carcinogenesis.

    abstract::The influence of the tumor promoter 2-acetylaminofluorene (2-AAF) on cell proliferation and on the epidermal growth factor receptor (EGFR) system was assessed in normal and nodular rat livers. DNA replication in vivo was inhibited below the detection level after 8d of dietary 2-AAF treatment of previously unexposed ra...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.2940100207

    authors: Strömblad S,Eriksson LC,Andersson G

    更新日期:1994-06-01 00:00:00

  • Differential expression of the O6-alkylguanine-DNA alkyltransferase gene in normal human breast and skin tissue: in situ mapping of cell type-specific expression.

    abstract::O6-Alkylguanine is a major toxic, mutagenic, and carcinogenic lesion in cellular DNA that is repaired by O6-alkylguanine-DNA alkyltransferase (ATase). The expression of this gene is directly related to the cellular sensitivity of alkylating agents, with levels of this protein varying widely among human organs, tumors,...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.2940120309

    authors: Wani G,D'Ambrosio SM

    更新日期:1995-03-01 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

  • Putative tumor suppressor gene SEL1L was downregulated by aberrantly upregulated hsa-mir-155 in human pancreatic ductal adenocarcinoma.

    abstract::Sel-1-like (SEL1L) is a putative tumor suppressor gene that is significantly downregulated in human pancreatic ductal adenocarcinoma (PDA). The mechanism of the downregulation is unclear. Here, we investigated whether aberrantly upregulated microRNAs (miRNAs) repressed the expression of SEL1L. From reported miRNA micr...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22023

    authors: Liu Q,Chen J,Wang J,Amos C,Killary AM,Sen S,Wei C,Frazier ML

    更新日期:2014-09-01 00:00:00

  • Association of ERCC1 polymorphisms and susceptibility to nasopharyngeal carcinoma.

    abstract::The normal function of excision repair cross complementing group 1 (ERCC1) is essential for maintaining genomic integrity and preventing cellular neoplastic transformation, and multiple studies have reported an association between ERCC1 polymorphisms and increased risk of cancers. To test whether the genetic variants ...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章,随机对照试验

    doi:10.1002/mc.20468

    authors: Yang ZH,Dai Q,Kong XL,Yang WL,Zhang L

    更新日期:2009-03-01 00:00:00

  • CD44/cellular prion protein interact in multidrug resistant breast cancer cells and correlate with responses to neoadjuvant chemotherapy in breast cancer patients.

    abstract::Multidrug resistance (MDR) is one of the most important factors leading to chemotherapeutic failure in patients with breast cancer. The invasive/metastatic ability of MDR cells is strengthened compared with their parental cells. However, the mechanisms underlying MDR have not been fully elucidated. We found that CD44 ...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22021

    authors: Cheng Y,Tao L,Xu J,Li Q,Yu J,Jin Y,Chen Q,Xu Z,Zou Q,Liu X

    更新日期:2014-09-01 00:00:00

  • Identification of RB and p53 mutations in mouse lymphoma cell lines.

    abstract::We analyzed the genomic structure and mRNA of the RB and p53 genes in four mouse lymphoid leukemia cell lines (DL-1, DL-5, DL-8, and DL-12). Although no gross structural alteration of the RB gene was observed in any cell line, abnormalities of RB mRNA were detected in at least two cell lines. RB mRNA expression was gr...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.2940040505

    authors: Murakami A,Tanaka H

    更新日期:1991-01-01 00:00:00

  • Cancer-bone microenvironmental interactions promotes STAT3 signaling.

    abstract::Prostate cancer (PCa) patients' mortality is mainly attributed to complications caused by metastasis of the tumor cells to organs critical for survival, such as bone. We hypothesized that PCa cell-bone interactions would promote paracrine signaling. A panel of PCa cell lines were cocultured with hydroxyapatite ([HA]; ...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.23019

    authors: Henderson VM,Hawsawi O,Burton LJ,Campbell T,Trice K,Dougan J,Howard SM,Odero-Marah VA

    更新日期:2019-08-01 00:00:00

  • Persistent infection of hepatitis B virus is involved in high rate of p16 methylation in hepatocellular carcinoma.

    abstract::High rate of chronic hepatitis B virus (HBV) infection and p16 promoter methylation were found in the majority of hepatocellular carcinoma (HCC). To investigate the potential linkage between high rate of p16 methylation and HBV infection, p16 methylation was detected with methylation-specific polymerase chain reaction...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20188

    authors: Jicai Z,Zongtao Y,Jun L,Haiping L,Jianmin W,Lihua H

    更新日期:2006-07-01 00:00:00

  • Regulation of keratinocyte growth factor expression in human endometrium: implications for hormonal carcinogenesis.

    abstract::Estrogen is thought to be an important etiologic agent in endometrial and breast cancers. However, the mechanism or mechanisms by which estrogen acts as a hormonal carcinogen are not well understood. We hypothesize that in response to chronic exposure to estrogens, human endometrial stromal fibroblasts (ESF) produce f...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/(sici)1098-2744(199812)23:4<217::aid-mc4>3

    authors: Li Y,Rinehart CA

    更新日期:1998-12-01 00:00:00

  • Involvement of Akt/NF-κB pathway in N6-isopentenyladenosine-induced apoptosis in human breast cancer cells.

    abstract::N(6)-isopentenyladenosine (i6A) inhibits the tumor cell growth by inducing cell apoptosis in various cancer cell lines. However, little is known regarding the mechanisms by which the drug induces cell apoptosis. In this study, we further explored the molecular mechanisms of i6A as an anticancer agent on a human breast...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20666

    authors: Laezza C,Malfitano AM,Di Matola T,Ricchi P,Bifulco M

    更新日期:2010-10-01 00:00:00

  • Mechanistic studies of the effects of the retinoid N-(4-hydroxyphenyl)retinamide on prostate cancer cell growth and apoptosis.

    abstract::To explore the mechanisms underlying the chemopreventive effects of the synthetic retinoid N-(4-hydroxyphenyl)retinamide (4-HPR) in prostate cancer, we evaluated the anti-proliferative and apoptosis-inducing effects of 4-HPR in the androgen-sensitive human prostate cancer cell line LNCaP. 4-HPR decreased the number of...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/(sici)1098-2744(199903)24:3<160::aid-mc2>3

    authors: Shen JC,Wang TT,Chang S,Hursting SD

    更新日期:1999-03-01 00:00:00

  • An in vitro system to characterize prostate cancer progression identified signaling required for self-renewal.

    abstract::Mutations in RB and PTEN are linked to castration resistance and poor prognosis in prostate cancer. Identification of genes that are regulated by these tumor suppressors in a context that recapitulates cancer progression may be beneficial for discovering novel therapeutic targets. Although various genetically engineer...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22444

    authors: Salah M,Nishimoto Y,Kohno S,Kondoh A,Kitajima S,Muranaka H,Nishiuchi T,Ibrahim A,Yoshida A,Takahashi C

    更新日期:2016-12-01 00:00:00

  • The effect of the JE (MCP-1) gene, which encodes monocyte chemoattractant protein-1, on the growth of HeLa cells and derived somatic-cell hybrids in nude mice.

    abstract::To investigate the effect of tumor-associated macrophages on the in vivo growth properties of cervical carcinoma cells, tumorigenic human papilloma virus (HPV) 18-positive HeLa cells were transfected with an expression vector harboring the cDNA for the macrophage chemoattractant protein-1 JE (MCP-1). Although the endo...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.2940140307

    authors: Kleine K,König G,Kreuzer J,Komitowski D,Zur Hausen H,Rösl F

    更新日期:1995-11-01 00:00:00