FoxM1 promotes β-catenin nuclear localization and controls Wnt target-gene expression and glioma tumorigenesis.


:Wnt/β-catenin signaling is essential for stem cell regulation and tumorigenesis, but its molecular mechanisms are not fully understood. Here, we report that FoxM1 is a downstream component of Wnt signaling and is critical for β-catenin transcriptional function in tumor cells. Wnt3a increases the level and nuclear translocation of FoxM1, which binds directly to β-catenin and enhances β-catenin nuclear localization and transcriptional activity. Genetic deletion of FoxM1 in immortalized neural stem cells abolishes β-catenin nuclear localization. FoxM1 mutations that disrupt the FoxM1-β-catenin interaction or FoxM1 nuclear import prevent β-catenin nuclear accumulation in tumor cells. FoxM1-β-catenin interaction controls Wnt target gene expression, is required for glioma formation, and represents a mechanism for canonical Wnt signaling during tumorigenesis.


Cancer Cell


Cancer cell


Zhang N,Wei P,Gong A,Chiu WT,Lee HT,Colman H,Huang H,Xue J,Liu M,Wang Y,Sawaya R,Xie K,Yung WK,Medema RH,He X,Huang S




Has Abstract


2011-10-18 00:00:00














  • Facilitating T Cell Infiltration in Tumor Microenvironment Overcomes Resistance to PD-L1 Blockade.

    abstract::Immune checkpoint blockade therapies fail to induce responses in the majority of cancer patients, so how to increase the objective response rate becomes an urgent challenge. Here, we demonstrate that sufficient T cell infiltration in tumor tissues is a prerequisite for response to PD-L1 blockade. Targeting tumors with...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: Tang H,Wang Y,Chlewicki LK,Zhang Y,Guo J,Liang W,Wang J,Wang X,Fu YX

    更新日期:2016-03-14 00:00:00

  • Hepatocyte necrosis induced by oxidative stress and IL-1 alpha release mediate carcinogen-induced compensatory proliferation and liver tumorigenesis.

    abstract::Hepatocyte I kappaB kinase beta (IKK beta) inhibits hepatocarcinogenesis by suppressing accumulation of reactive oxygen species (ROS) and liver damage, whereas JNK1 activation promotes ROS accumulation, liver damage, and carcinogenesis. We examined whether hepatocyte p38 alpha, found to inhibit liver carcinogenesis, a...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: Sakurai T,He G,Matsuzawa A,Yu GY,Maeda S,Hardiman G,Karin M

    更新日期:2008-08-12 00:00:00

  • Escape from Cbl-mediated downregulation: a recurrent theme for oncogenic deregulation of receptor tyrosine kinases.

    abstract::Deregulation of growth factor receptor tyrosine kinases (RTKs) is linked to a large number of malignancies. This occurs through a variety of mechanisms that result in enhanced activity of the receptor. Considerable evidence now supports the idea that loss of negative regulation plays an important role in receptor dere...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: Peschard P,Park M

    更新日期:2003-06-01 00:00:00

  • TAK1 suppresses a NEMO-dependent but NF-kappaB-independent pathway to liver cancer.

    abstract::The MAP3-kinase TGF-beta-activated kinase 1 (TAK1) critically modulates innate and adaptive immune responses and connects cytokine stimulation with activation of inflammatory signaling pathways. Here, we report that conditional ablation of TAK1 in liver parenchymal cells (hepatocytes and cholangiocytes) causes hepatoc...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: Bettermann K,Vucur M,Haybaeck J,Koppe C,Janssen J,Heymann F,Weber A,Weiskirchen R,Liedtke C,Gassler N,Müller M,de Vos R,Wolf MJ,Boege Y,Seleznik GM,Zeller N,Erny D,Fuchs T,Zoller S,Cairo S,Buendia MA,Prinz M,A

    更新日期:2010-05-18 00:00:00

  • ERK-MAPK signaling opposes Rho-kinase to promote endothelial cell survival and sprouting during angiogenesis.

    abstract::Inhibition of ERK-MAPK signaling by expression of dominant-negative MEK1 in the tumor vasculature suppresses angiogenesis and tumor growth. In an organotypic tissue culture angiogenesis assay, ERK-MAPK inhibition during the migratory phase results in loss of bipolarity, detachment, and cell death of isolated endotheli...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: Mavria G,Vercoulen Y,Yeo M,Paterson H,Karasarides M,Marais R,Bird D,Marshall CJ

    更新日期:2006-01-01 00:00:00

  • Singling Out Chromosome Gains in Tumor Evolution.

    abstract::In this issue of Cancer Cell, Sheltzer et al. shed new light on Theodor Boveri's century-old hypothesis by demonstrating that aneuploidy characterized by single-chromosome gains acts to suppress tumorigenesis and that aneuploidy itself is a nidus for genomic instability. ...

    journal_title:Cancer cell

    pub_type: 评论,杂志文章


    authors: Naylor RM,van Deursen JM

    更新日期:2017-02-13 00:00:00

  • The cyclin-like protein Spy1 regulates growth and division characteristics of the CD133+ population in human glioma.

    abstract::The heterogeneity of brain cancers, as most solid tumors, complicates diagnosis and treatment. Identifying and targeting populations of cells driving tumorigenesis is a top priority for the cancer biology field. This is not a trivial task; considerable variance exists in the driving mutations, identifying markers, and...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: Lubanska D,Market-Velker BA,deCarvalho AC,Mikkelsen T,Fidalgo da Silva E,Porter LA

    更新日期:2014-01-13 00:00:00

  • Mdm2 is critically and continuously required to suppress lethal p53 activity in vivo.

    abstract::There is currently much interest in the idea of restoring p53 activity in tumor cells by inhibiting Hdm2/Mdm2. However, it has remained unclear whether this would also activate p53 in normal cells. Using a switchable endogenous p53 mouse model, which allows rapid and reversible toggling of p53 status between wild-type...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: Ringshausen I,O'Shea CC,Finch AJ,Swigart LB,Evan GI

    更新日期:2006-12-01 00:00:00

  • Prune cAMP phosphodiesterase binds nm23-H1 and promotes cancer metastasis.

    abstract::We identify a new enzymatic activity underlying metastasis in breast cancer and describe its susceptibility to therapeutic inhibition. We show that human prune (h-prune), a phosphoesterase DHH family appertaining protein, has a hitherto unrecognized cyclic nucleotide phosphodiesterase activity effectively suppressed b...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: D'Angelo A,Garzia L,André A,Carotenuto P,Aglio V,Guardiola O,Arrigoni G,Cossu A,Palmieri G,Aravind L,Zollo M

    更新日期:2004-02-01 00:00:00

  • Absence of telomerase and shortened telomeres have minimal effects on skin and pancreatic carcinogenesis elicited by viral oncogenes.

    abstract::The telomere-stabilizing enzyme telomerase is induced in tumors and functionally associated with unlimited replicative potential. To further explore its necessity, transgenic mice expressing SV40 or HPV16 oncogenes, which elicit carcinomas in pancreas and skin, respectively, were rendered telomerase-deficient. Absence...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: Argilla D,Chin K,Singh M,Hodgson JG,Bosenberg M,de Solórzano CO,Lockett S,DePinho RA,Gray J,Hanahan D

    更新日期:2004-10-01 00:00:00

  • A radical role for p38 MAPK in tumor initiation.

    abstract::It is established that p38 MAPK can negatively regulate tumorigenesis, but the mechanism is incompletely understood. A new study in this issue of Cancer Cell shows that p38 MAP kinase plays a selective role in tumor initiation mediated by oxidative stress. ...

    journal_title:Cancer cell

    pub_type: 评论,杂志文章


    authors: Kennedy NJ,Cellurale C,Davis RJ

    更新日期:2007-02-01 00:00:00

  • Neuroblastoma Metastases: Leveraging the Avian Neural Crest.

    abstract::Neuroblastoma, an embryonal cancer of neural crest origin, shows metastases frequently at diagnosis. In this issue of Cancer Cell, Delloye-Bourgeois and colleagues demonstrate that neuroblastoma cell lines and patient-derived xenografts engraft and adopt a metastatic program in chick embryos. They identify Sema3C as a...

    journal_title:Cancer cell

    pub_type: 评论,杂志文章


    authors: Zheng T,Ménard M,Weiss WA

    更新日期:2017-10-09 00:00:00

  • Metabolic Inflammation-Associated IL-17A Causes Non-alcoholic Steatohepatitis and Hepatocellular Carcinoma.

    abstract::Obesity increases hepatocellular carcinoma (HCC) risks via unknown mediators. We report that hepatic unconventional prefoldin RPB5 interactor (URI) couples nutrient surpluses to inflammation and non-alcoholic steatohepatitis (NASH), a common cause of HCC. URI-induced DNA damage in hepatocytes triggers inflammation via...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: Gomes AL,Teijeiro A,Burén S,Tummala KS,Yilmaz M,Waisman A,Theurillat JP,Perna C,Djouder N

    更新日期:2016-07-11 00:00:00

  • Long Noncoding RNAs in Cancer Pathways.

    abstract::Genome-wide cancer mutation analyses are revealing an extensive landscape of functional mutations within the noncoding genome, with profound effects on the expression of long noncoding RNAs (lncRNAs). While the exquisite regulation of lncRNA transcription can provide signals of malignant transformation, we now underst...

    journal_title:Cancer cell

    pub_type: 杂志文章,评审


    authors: Schmitt AM,Chang HY

    更新日期:2016-04-11 00:00:00

  • Alternative and aberrant splicing of MDM2 mRNA in human cancer.

    abstract::MDM2 has been characterized as a protein that binds to and facilitates degradation of the tumor suppressor p53. Interestingly, more than 40 different splice variants of MDM2 transcripts have been identified both in tumors and normal tissues, and the majority of these variants do not contain sequence encoding the p53 b...

    journal_title:Cancer cell

    pub_type: 杂志文章,评审


    authors: Bartel F,Taubert H,Harris LC

    更新日期:2002-07-01 00:00:00

  • BMP meets AML: induction of BMP signaling by a novel fusion gene promotes pediatric acute leukemia.

    abstract::In this issue of Cancer Cell, Gruber et al. report that a significant proportion of children with acute megakaryoblastic leukemia acquire a translocation that confers enhanced BMP signaling and promotes self-renewal of hematopoietic progenitors. This study presents novel therapeutic targets that may lead to improved t...

    journal_title:Cancer cell

    pub_type: 评论,杂志文章


    authors: Crispino JD,Le Beau MM

    更新日期:2012-11-13 00:00:00

  • Targeting the Senescence-Overriding Cooperative Activity of Structurally Unrelated H3K9 Demethylases in Melanoma.

    abstract::Oncogene-induced senescence, e.g., in melanocytic nevi, terminates the expansion of pre-malignant cells via transcriptional silencing of proliferation-related genes due to decoration of their promoters with repressive trimethylated histone H3 lysine 9 (H3K9) marks. We show here that structurally distinct H3K9-active d...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: Yu Y,Schleich K,Yue B,Ji S,Lohneis P,Kemper K,Silvis MR,Qutob N,van Rooijen E,Werner-Klein M,Li L,Dhawan D,Meierjohann S,Reimann M,Elkahloun A,Treitschke S,Dörken B,Speck C,Mallette FA,Zon LI,Holmen SL,Peeper DS

    更新日期:2018-02-12 00:00:00

  • ERK Activation Globally Downregulates miRNAs through Phosphorylating Exportin-5.

    abstract::MicroRNAs (miRNA) are mostly downregulated in cancer. However, the mechanism underlying this phenomenon and the precise consequence in tumorigenesis remain obscure. Here we show that ERK suppresses pre-miRNA export from the nucleus through phosphorylation of exportin-5 (XPO5) at T345/S416/S497. After phosphorylation b...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: Sun HL,Cui R,Zhou J,Teng KY,Hsiao YH,Nakanishi K,Fassan M,Luo Z,Shi G,Tili E,Kutay H,Lovat F,Vicentini C,Huang HL,Wang SW,Kim T,Zanesi N,Jeon YJ,Lee TJ,Guh JH,Hung MC,Ghoshal K,Teng CM,Peng Y,Croce CM

    更新日期:2016-11-14 00:00:00

  • Twist1-induced invadopodia formation promotes tumor metastasis.

    abstract::The Twist1 transcription factor is known to promote tumor metastasis and induce Epithelial-Mesenchymal Transition (EMT). Here, we report that Twist1 is capable of promoting the formation of invadopodia, specialized membrane protrusions for extracellular matrix degradation. Twist1 induces PDGFRα expression, which in tu...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: Eckert MA,Lwin TM,Chang AT,Kim J,Danis E,Ohno-Machado L,Yang J

    更新日期:2011-03-08 00:00:00

  • Tobacco smoke promotes lung tumorigenesis by triggering IKKbeta- and JNK1-dependent inflammation.

    abstract::Chronic exposure to tobacco smoke, which contains over 60 tumor-initiating carcinogens, is the major risk factor for development of lung cancer, accounting for a large portion of cancer-related deaths worldwide. It is well established that tobacco smoke is a tumor initiator, but we asked whether it also acts as a tumo...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: Takahashi H,Ogata H,Nishigaki R,Broide DH,Karin M

    更新日期:2010-01-19 00:00:00

  • Impairment of cytoplasmic eIF6 activity restricts lymphomagenesis and tumor progression without affecting normal growth.

    abstract::Eukaryotic Initiation Factor 6 (eIF6) controls translation by regulating 80S subunit formation. eIF6 is overexpressed in tumors. Here, we demonstrate that eIF6 inactivation delays tumorigenesis and reduces tumor growth in vivo. eIF6(+/-) mice resist to Myc-induced lymphomagenesis and have prolonged tumor-free survival...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: Miluzio A,Beugnet A,Grosso S,Brina D,Mancino M,Campaner S,Amati B,de Marco A,Biffo S

    更新日期:2011-06-14 00:00:00

  • Erk Negative Feedback Control Enables Pre-B Cell Transformation and Represents a Therapeutic Target in Acute Lymphoblastic Leukemia.

    abstract::Studying mechanisms of malignant transformation of human pre-B cells, we found that acute activation of oncogenes induced immediate cell death in the vast majority of cells. Few surviving pre-B cell clones had acquired permissiveness to oncogenic signaling by strong activation of negative feedback regulation of Erk si...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: Shojaee S,Caeser R,Buchner M,Park E,Swaminathan S,Hurtz C,Geng H,Chan LN,Klemm L,Hofmann WK,Qiu YH,Zhang N,Coombes KR,Paietta E,Molkentin J,Koeffler HP,Willman CL,Hunger SP,Melnick A,Kornblau SM,Müschen M

    更新日期:2015-07-13 00:00:00

  • The oncoprotein gankyrin binds to MDM2/HDM2, enhancing ubiquitylation and degradation of p53.

    abstract::Gankyrin is an ankyrin repeat oncoprotein commonly overexpressed in hepatocellular carcinomas. Gankyrin interacts with the S6 proteasomal ATPase and accelerates the degradation of the tumor suppressor Rb. We show here that gankyrin has an antiapoptotic activity in cells exposed to DNA damaging agents. Downregulation o...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: Higashitsuji H,Higashitsuji H,Itoh K,Sakurai T,Nagao T,Sumitomo Y,Masuda T,Dawson S,Shimada Y,Mayer RJ,Fujita J

    更新日期:2005-07-01 00:00:00

  • E2F1-regulated microRNAs impair TGFbeta-dependent cell-cycle arrest and apoptosis in gastric cancer.

    abstract::Deregulation of E2F1 activity and resistance to TGFbeta are hallmarks of gastric cancer. MicroRNAs (miRNAs) are small noncoding RNAs frequently misregulated in human malignancies. Here we provide evidence that the miR-106b-25 cluster, upregulated in a subset of human gastric tumors, is activated by E2F1 in parallel wi...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: Petrocca F,Visone R,Onelli MR,Shah MH,Nicoloso MS,de Martino I,Iliopoulos D,Pilozzi E,Liu CG,Negrini M,Cavazzini L,Volinia S,Alder H,Ruco LP,Baldassarre G,Croce CM,Vecchione A

    更新日期:2008-03-01 00:00:00

  • Neutrophils Oppose Uterine Epithelial Carcinogenesis via Debridement of Hypoxic Tumor Cells.

    abstract::Polymorphonuclear neutrophils (PMNs) are largely considered to foster cancer development despite wielding an arsenal of cytotoxic agents. Using a mouse model of PTEN-deficient uterine cancer, we describe a surprising inhibitory role for PMNs in epithelial carcinogenesis. By inducing tumor cell detachment from the base...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: Blaisdell A,Crequer A,Columbus D,Daikoku T,Mittal K,Dey SK,Erlebacher A

    更新日期:2015-12-14 00:00:00

  • Kidney cancer: now available in a new flavor.

    abstract::The role of the von Hippel-Lindau tumor suppressor protein (pVHL) in kidney cancer has provided a rationale for treating this disease with hypoxia-inducible factor (HIF) antagonists. In this issue, Simon and coworkers show that the molecular signature of VHL(-/-) kidney cancers is profoundly influenced by whether they...

    journal_title:Cancer cell

    pub_type: 评论,杂志文章


    authors: Kaelin WG Jr

    更新日期:2008-12-09 00:00:00

  • New Views into the Genetic Landscape of Metastatic Breast Cancer.

    abstract::Whether metastasis-specific genetic alterations exist remains controversial. The study by Yates et al. in this issue of Cancer Cell provides evidence that metastases emerge late during primary breast cancer progression and that additional driver mutations are often acquired, posing both challenges and opportunities fo...

    journal_title:Cancer cell

    pub_type: 评论,杂志文章


    authors: Zhao X,Powers S

    更新日期:2017-08-14 00:00:00

  • Impact of COVID-19 Pandemic on Cancer Research.

    abstract::The COVID-19 pandemic is profoundly changing cancer researchers and cancer research. Leaders from different fields and at different career stages share their perspectives. ...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: Zon L,Gomes AP,Cance WG,Ribas A,Tuveson D,Postel-Vinay S,Massard C,Barlési F

    更新日期:2020-11-09 00:00:00

  • miR-30b/30d regulation of GalNAc transferases enhances invasion and immunosuppression during metastasis.

    abstract::To metastasize, a tumor cell must acquire abilities such as the capacity to colonize new tissue and evade immune surveillance. Recent evidence suggests that microRNAs can promote the evolution of malignant behaviors by regulating multiple targets. We performed a microRNA analysis of human melanoma, a highly invasive c...

    journal_title:Cancer cell

    pub_type: 杂志文章


    authors: Gaziel-Sovran A,Segura MF,Di Micco R,Collins MK,Hanniford D,Vega-Saenz de Miera E,Rakus JF,Dankert JF,Shang S,Kerbel RS,Bhardwaj N,Shao Y,Darvishian F,Zavadil J,Erlebacher A,Mahal LK,Osman I,Hernando E

    更新日期:2011-07-12 00:00:00

  • Methylome alterations "mark" new therapeutic opportunities in glioblastoma.

    abstract::In this issue of Cancer Cell, Sturm et al. report that global DNA methylation patterns in glioblastoma multiforme divide adult and pediatric tumors into subgroups that have characteristic DNA mutations, mRNA profiles, and most importantly, different clinical behaviors. These findings suggest novel opportunities for th...

    journal_title:Cancer cell

    pub_type: 评论,杂志文章


    authors: Raabe EH,Eberhart CG

    更新日期:2012-10-16 00:00:00