Regulation of Axl receptor tyrosine kinase expression by miR-34a and miR-199a/b in solid cancer.


:Axl is a receptor that induces proliferation, migration and invasion in cancer. In this study, we show that specific microRNAs (miRNAs) target the 3'-UTR of Axl. Luciferase-reporter assays with wild-type and deleted miR-34 and miR-199a/b seed sequences of Axl 3'-UTR confirmed the specificity of targeting. An inverse correlation between Axl protein and miR-34a expression in a panel of non-small cell lung cancer (NSCLC), colorectal cancer (CRC) and breast cancer (BRC) cell lines was observed, while miR-199a/b expression was completely suppressed. Pre-miR transfection inhibited in vitro migration and invasion and, in vivo, reduced the number of distant lung- or liver-metastases in a chorion-allantoic-membrane (CAM) assay. Moreover, methylation-specific PCR on bisulfite-converted DNA obtained from the cell lines showed that the miR-34a promoter methylation status was inversely correlated with its expression, and that miR-199a/b promoter regions were methylated in all cells tested. In a panel of NSCLC tissues (n=44), miR-34a and miR-199a/b were found to be downregulated and significantly co-expressed. A lower expression of all three miRs was significantly associated with squamous histotypes, and, in a preliminary series, NSCLC patients with miR-34a upregulation showed a positive association towards a longer survival. These results indicate that Axl receptor expression can be regulated by miR-34a and miR-199a/b, which are suppressed by promoter methylation in solid cancer cells.






Mudduluru G,Ceppi P,Kumarswamy R,Scagliotti GV,Papotti M,Allgayer H




Has Abstract


2011-06-23 00:00:00
















  • Viral rel and cellular rel associate with cellular proteins in transformed and normal cells.

    abstract::The rel oncogene from the avian reticuloendotheliosis virus strain T is a 59 kd phosphoprotein localized primarily to the cytoplasm of transformed cells. Recently, the v-rel protein was shown to associate with several cellular proteins with molecular weights of 124 kd, 115 kd, and 36 kd. We have analysed the subcellul...


    pub_type: 杂志文章


    authors: Morrison LE,Kabrun N,Mudri S,Hayman MJ,Enrietto PJ

    更新日期:1989-06-01 00:00:00

  • Smad3 regulates E-cadherin via miRNA-200 pathway.

    abstract::To identify potential microRNA (miRNA) links between Smad3, a mediator of TGF-β (transforming growth factor-β) signaling, and E-cadherin, we characterized the miRNA profiles of two gastric cancer cell lines: SNU484-LPCX, which does not express Smad3, and SNU484-Smad3, in which Smad3 is overexpressed. We found that amo...


    pub_type: 杂志文章


    authors: Ahn SM,Cha JY,Kim J,Kim D,Trang HT,Kim YM,Cho YH,Park D,Hong S

    更新日期:2012-06-21 00:00:00

  • Fas signaling promotes motility and metastasis through epithelial-mesenchymal transition in gastrointestinal cancer.

    abstract::Fas signaling was reported to participate in cell apoptosis. However, this pathway has also been shown to promote tumor cell motility, leading to the hypothesis that Fas signaling may induce epithelial-mesenchymal transition (EMT) to promote metastasis. The effects of Fas-ligand (FasL) treatment and inhibition of Fas ...


    pub_type: 杂志文章


    authors: Zheng HX,Cai YD,Wang YD,Cui XB,Xie TT,Li WJ,Peng L,Zhang Y,Wang ZQ,Wang J,Jiang B

    更新日期:2013-02-28 00:00:00

  • A functional analysis of PCNA-binding peptides derived from protein sequence, interaction screening and rational design.

    abstract::Proliferating cell nuclear antigen (PCNA) has no intrinsic enzymatic function, but functions as a sliding platform to mediate protein interactions with the DNA strand. Many proteins interact with PCNA through a small conserved motif with consensus QxxLxxFF. This work uses Schizosaccharomyces pombe and human cells to a...


    pub_type: 杂志文章


    authors: Warbrick E

    更新日期:2006-05-11 00:00:00

  • Selective loss of endogenous p21waf1/cip1 induction underlies the G1 checkpoint defect of monomeric p53 proteins.

    abstract::Wild-type p53 protein displays a spectrum of activities including the ability to suppress transformed cell growth to direct apoptotic cell death and to mediate G1 checkpoint in response to cellular DNA damage. Earlier work showed that a self-association defective p53 protein retained transformation suppressor activity...


    pub_type: 杂志文章


    authors: Tarunina M,Grimaldi M,Ruaro E,Pavlenko M,Schneider C,Jenkins JR

    更新日期:1996-08-01 00:00:00

  • Activation of the Wnt pathway in non small cell lung cancer: evidence of dishevelled overexpression.

    abstract::Non small cell lung cancer (NSCLC) is the leading cause of cancer deaths in the United States and worldwide. Unfortunately, standard therapies remain inadequate. An increased understanding of the molecular biology of lung cancer biology is required to develop more effective new therapies. In this report, we show that ...


    pub_type: 杂志文章


    authors: Uematsu K,He B,You L,Xu Z,McCormick F,Jablons DM

    更新日期:2003-10-16 00:00:00

  • RET cooperates with RB/p53 inactivation in a somatic multi-step model for murine thyroid cancer.

    abstract::Mice bred to carry germline Rb and p53 null alleles are associated with a tumor spectrum that overlaps with the inherited multiple endocrine neoplasia-1 (MEN1) and MEN2 syndromes in humans, including medullary thyroid cancer (MTC). To study the genetic basis for these tumors, we microdissected MTC specimens or obtaine...


    pub_type: 杂志文章


    authors: Coxon AB,Ward JM,Geradts J,Otterson GA,Zajac-Kaye M,Kaye FJ

    更新日期:1998-09-24 00:00:00

  • Snail is a repressor of RKIP transcription in metastatic prostate cancer cells.

    abstract::Diminished expression of the metastasis suppressor protein RKIP was previously reported in a number of cancers. The underlying mechanism remains unknown. Here, we show that the expression of RKIP negatively correlates with that of Snail zinc-transcriptional repressor, a key modulator of normal and neoplastic epithelia...


    pub_type: 杂志文章


    authors: Beach S,Tang H,Park S,Dhillon AS,Keller ET,Kolch W,Yeung KC

    更新日期:2008-04-03 00:00:00

  • Fibroblasts drive an immunosuppressive and growth-promoting microenvironment in breast cancer via secretion of Chitinase 3-like 1.

    abstract::Cancer-Associated Fibroblasts (CAFs) are the most prominent stromal cell type in breast tumors. CAFs promote tumor growth and metastasis by multiple mechanisms, including by mediating tumor-promoting inflammation. Immune modulation in the tumor microenvironment plays a central role in determining disease outcome. Howe...


    pub_type: 杂志文章


    authors: Cohen N,Shani O,Raz Y,Sharon Y,Hoffman D,Abramovitz L,Erez N

    更新日期:2017-08-01 00:00:00

  • Artemis is a negative regulator of p53 in response to oxidative stress.

    abstract::Artemis is a multifunctional phospho-protein with roles in V(D)J recombination, repair of double-strand breaks by nonhomologous end-joining and regulation of cell-cycle checkpoints after DNA damage. Here, we describe a new function of Artemis as a negative regulator of p53 in response to oxidative stress in both prima...


    pub_type: 杂志文章


    authors: Zhang X,Zhu Y,Geng L,Wang H,Legerski RJ

    更新日期:2009-06-04 00:00:00

  • Lung-specific expression of human mutant p53-273H is associated with a high frequency of lung adenocarcinoma in transgenic mice.

    abstract::To investigate the tumorigenic potential of mutant p53 when selectively expressed in lung tissue, a transgenic mouse model was developed in which a mutant form of p53 (p53-273H) was placed under the transcriptional control of the lung-specific human surfactant protein C (SP-C) promoter. Two founder mice were identifie...


    pub_type: 杂志文章


    authors: Duan W,Ding H,Subler MA,Zhu WG,Zhang H,Stoner GD,Windle JJ,Otterson GA,Villalona-Calero MA

    更新日期:2002-11-07 00:00:00

  • Role of MMP-2 in the regulation of IL-6/Stat3 survival signaling via interaction with α5β1 integrin in glioma.

    abstract::Matrix metalloproteinase-2 (MMP-2) has pivotal role in the degradation of extracellular matrix, and thereby enhances the invasive, proliferative and metastatic potential in cancer. Knockdown of MMP-2 using MMP-2 small interfering RNA (pM) in human glioma xenograft cell lines 4910 and 5310 decreased cell proliferation ...


    pub_type: 杂志文章


    authors: Kesanakurti D,Chetty C,Dinh DH,Gujrati M,Rao JS

    更新日期:2013-01-17 00:00:00

  • Cytoplasmic localization of p120ctn and E-cadherin loss characterize lobular breast carcinoma from preinvasive to metastatic lesions.

    abstract::Accumulating evidences indicate that p120 catenin, a member of the E-cadherin (E-CD)/catenin adhesion complex, plays a role in tumor invasion. To establish the expression pattern of p120 in breast cancer, we analysed 326 breast tissue biopsies by tissue microarray. Most of the lobular tumors (88%) showed exclusive cyt...


    pub_type: 杂志文章


    authors: Sarrió D,Pérez-Mies B,Hardisson D,Moreno-Bueno G,Suárez A,Cano A,Martín-Pérez J,Gamallo C,Palacios J

    更新日期:2004-04-22 00:00:00

  • Direct integrin alphavbeta6-ERK binding: implications for tumour growth.

    abstract::Blockade of the mitogen-activated protein (MAP) kinase pathway suppresses growth of colon cancer in vivo. Here we demonstrate a direct link between the extracellular signal-regulated kinase ERK2 and the growth-promoting cell adhesion molecule, integrin alphavbeta6, in colon cancer cells. Down-regulation of beta6 integ...


    pub_type: 杂志文章


    authors: Ahmed N,Niu J,Dorahy DJ,Gu X,Andrews S,Meldrum CJ,Scott RJ,Baker MS,Macreadie IG,Agrez MV

    更新日期:2002-02-21 00:00:00

  • Downregulation of ceramide synthase-6 during epithelial-to-mesenchymal transition reduces plasma membrane fluidity and cancer cell motility.

    abstract::Epithelial-to-mesenchymal transition (EMT) promotes cell motility, which is important for the metastasis of malignant cells, and blocks CD95-mediated apoptotic signaling triggered by immune cells and chemotherapeutic regimens. CD95L, the cognate ligand of CD95, can be cleaved by metalloproteases and released as a solu...


    pub_type: 杂志文章


    authors: Edmond V,Dufour F,Poiroux G,Shoji K,Malleter M,Fouqué A,Tauzin S,Rimokh R,Sergent O,Penna A,Dupuy A,Levade T,Theret N,Micheau O,Ségui B,Legembre P

    更新日期:2015-02-19 00:00:00

  • DNA: leukemia's secret weapon of bone mass destruction.

    abstract::Interaction of tumour cells with their microenvironment impacts on all aspects of cancer, ranging from development through to treatment response. In this issue, Dvorak and colleagues(1) reveal a novel tumour/microenvironment relationship that may drive leukemia pathogenesis. Specifically, they find that leukemic cells...


    pub_type: 评论,杂志文章


    authors: Tait S

    更新日期:2013-10-31 00:00:00

  • Snail silencing effectively suppresses tumour growth and invasiveness.

    abstract::The transcription factor Snail has been recently proposed as an important mediator of tumour invasion because of its role in downregulation of E-cadherin and induction of epithelial-mesenchymal transitions (EMT). This behaviour has led to the consideration of Snail as a potential therapeutic target to block tumour pro...


    pub_type: 杂志文章


    authors: Olmeda D,Jordá M,Peinado H,Fabra A,Cano A

    更新日期:2007-03-22 00:00:00

  • Hypermethylated gene ANKDD1A is a candidate tumor suppressor that interacts with FIH1 and decreases HIF1α stability to inhibit cell autophagy in the glioblastoma multiforme hypoxia microenvironment.

    abstract::Ectopic epigenetic mechanisms play important roles in facilitating tumorigenesis. Here, we first demonstrated that ANKDD1A is a functional tumor suppressor gene, especially in the hypoxia microenvironment. ANKDD1A directly interacts with FIH1 and inhibits the transcriptional activity of HIF1α by upregulating FIH1. In ...


    pub_type: 杂志文章


    authors: Feng J,Zhang Y,She X,Sun Y,Fan L,Ren X,Fu H,Liu C,Li P,Zhao C,Liu Q,Liu Q,Li G,Wu M

    更新日期:2019-01-01 00:00:00

  • Identification of genes associated with tumorigenesis and metastatic potential of hypopharyngeal cancer by microarray analysis.

    abstract::Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer among men in the developed world. There is a need, for both clinical and scientific reasons, to find markers to identify patients with aggressive disease as early as possible, and to understand the events leading to malignant transformation ...


    pub_type: 杂志文章


    authors: Cromer A,Carles A,Millon R,Ganguli G,Chalmel F,Lemaire F,Young J,Dembélé D,Thibault C,Muller D,Poch O,Abecassis J,Wasylyk B

    更新日期:2004-04-01 00:00:00

  • Characterization of VIK-1: a new Vav-interacting Kruppel-like protein.

    abstract::Binding partners of the Src homology domains of Vav-1 were characterized by a two-hybrid screening of a Jurkat cell cDNA library. One of the isolated clones encoded a new protein named VIK that belongs to the Kruppel-like zinc-finger gene family. Genome mapping showed that a single gene positioned at chromosome 7q22.1...


    pub_type: 杂志文章


    authors: Houlard M,Romero-Portillo F,Germani A,Depaux A,Regnier-Ricard F,Gisselbrecht S,Varin-Blank N

    更新日期:2005-01-06 00:00:00

  • miRNA let-7c promotes granulocytic differentiation in acute myeloid leukemia.

    abstract::MicroRNAs (miRNAs), small non-coding RNAs that regulate gene expression post-transcriptionally, are involved in many complex cellular processes. Several miRNAs are differentially expressed in hematopoietic tissues and play important roles in normal differentiation, but, when aberrantly regulated, contribute to the abn...


    pub_type: 杂志文章


    authors: Pelosi A,Careccia S,Lulli V,Romania P,Marziali G,Testa U,Lavorgna S,Lo-Coco F,Petti MC,Calabretta B,Levrero M,Piaggio G,Rizzo MG

    更新日期:2013-08-01 00:00:00

  • Cis/trans-activation of the interleukin-9 receptor gene in an HTLV-I-transformed human lymphocytic cell.

    abstract::The MT-2 cell-line, which had been established through in vitro cell to cell transmission of human T-cell leukemia virus type I (HTLV-I) among human primary lymphocytes, was shown to possess multiple copies of integrated proviruses, including defective proviral genomes. By analysing a genomic clone, we identified the ...


    pub_type: 杂志文章


    authors: Kubota S,Siomi H,Hatanaka M,Pomerantz RJ

    更新日期:1996-04-04 00:00:00

  • Hormonal modulation of ESR1 mutant metastasis.

    abstract::Estrogen receptor alpha gene (ESR1) mutations occur frequently in ER-positive metastatic breast cancer, and confer clinical resistance to aromatase inhibitors. Expression of the ESR1 Y537S mutation induced an epithelial-mesenchymal transition (EMT) with cells exhibiting enhanced migration and invasion potential in vit...


    pub_type: 杂志文章


    authors: Gu G,Tian L,Herzog SK,Rechoum Y,Gelsomino L,Gao M,Du L,Kim JA,Dustin D,Lo HC,Beyer AR,Edwards DG,Gonzalez T,Tsimelzon A,Huang HJ,Fernandez NM,Grimm SL,Hilsenbeck SG,Liu D,Xu J,Alaniz A,Li S,Mills GB,Janku F

    更新日期:2020-12-15 00:00:00

  • Functional expression of CXCR4 (CD184) on small-cell lung cancer cells mediates migration, integrin activation, and adhesion to stromal cells.

    abstract::Small-cell lung cancer (SCLC) is an aggressive, rapidly metastasizing neoplasm. The chemokine stromal cell-derived factor-1 (SDF-1/CXCL12) is constitutively secreted by marrow stromal cells and plays a key role for homing of hematopoietic cells to the marrow. Here, we report that tumor cells from patients with SCLC ex...


    pub_type: 杂志文章


    authors: Burger M,Glodek A,Hartmann T,Schmitt-Gräff A,Silberstein LE,Fujii N,Kipps TJ,Burger JA

    更新日期:2003-11-06 00:00:00

  • Involvement of matrix metalloproteinase-13 in stromal-cell-derived factor 1 alpha-directed invasion of human basal cell carcinoma cells.

    abstract::Basal cell carcinoma (BCC) is one of the most common skin neoplasms in humans and is usually characterized by local aggressiveness with little metastatic potential, although deep invasion, recurrence, and regional and distant metastases may occur. Here, we studied the mechanism of BCC invasion. We found that human BCC...


    pub_type: 杂志文章


    authors: Chu CY,Cha ST,Chang CC,Hsiao CH,Tan CT,Lu YC,Jee SH,Kuo ML

    更新日期:2007-04-12 00:00:00

  • Systems biology analysis of G protein and MAP kinase signaling in yeast.

    abstract::Approximately a third of all drugs act by binding directly to cell surface receptors coupled to G proteins. Other drugs act indirectly on these same pathways, for example, by inhibiting neurotransmitter reuptake or by blocking the inactivation of intracellular second messengers. These drugs have revolutionized the tre...


    pub_type: 杂志文章,评审


    authors: Hao N,Behar M,Elston TC,Dohlman HG

    更新日期:2007-05-14 00:00:00

  • Expression of Bcl-XS alters cytokinetics and decreases clonogenic survival in K12 rat colon carcinoma cells.

    abstract::bcl-XS, a member of the bcl-2 family, has been shown to induce and/or sensitize some cells to undergo programmed cell death, and to negate the anti-apoptotic activity of bcl-XL and bcl-2 by mechanisms which are still uncertain. To help understand these mechanisms we have established stable derivatives of the K12 rat c...


    pub_type: 杂志文章


    authors: Fridman JS,Rehemtulla A,Hofmann A,Blau HM,Maybaum J

    更新日期:1998-12-10 00:00:00

  • Mechanisms of the androgen receptor splicing in prostate cancer cells.

    abstract::Prostate tumors develop resistance to androgen deprivation therapy (ADT) by multiple mechanisms, one of which is to express constitutively active androgen receptor (AR) splice variants lacking the ligand-binding domain. AR splice variant 7 (AR-V7, also termed AR3) is the most abundantly expressed variant that drives p...


    pub_type: 杂志文章


    authors: Liu LL,Xie N,Sun S,Plymate S,Mostaghel E,Dong X

    更新日期:2014-06-12 00:00:00

  • Alterations in the common fragile site gene Parkin in ovarian and other cancers.

    abstract::The cloning and characterization of the common fragile site (CFS) FRA6E (6q26) identified Parkin, the gene involved in the pathogenesis of many cases of juvenile, early-onset and, rarely, late-onset Parkinson's disease, as the third large gene to be localized within a large CFS. Initial analyses of Parkin indicated th...


    pub_type: 杂志文章


    authors: Denison SR,Wang F,Becker NA,Schüle B,Kock N,Phillips LA,Klein C,Smith DI

    更新日期:2003-11-13 00:00:00

  • Evidence for human DNA-mediated transfer of the suppressed phenotype into malignant Chinese hamster cells.

    abstract::Genetic suppression of the neoplastic phenotype has been demonstrated in somatic cell hybrids between tumor and normal cells. Suppression in whole-cell and microcell hybrids cannot, as yet, be attributed to specific elements defined at the molecular level. To identify a gene capable of suppressing the neoplastic pheno...


    pub_type: 杂志文章


    authors: Schäfer R,Nirkko AC,Ambühl PM,Grzeschik KH,Schwarte-Waldhoff I

    更新日期:1991-12-01 00:00:00