Nutlin-3 inhibits epithelial-mesenchymal transition by interfering with canonical transforming growth factor-β1-Smad-Snail/Slug axis.

Abstract:

:Enormous efforts have been made to explore small molecules that interfere with the TGF-β signaling pathway, so as to inhibit EMT and the cancer metastasis, but few agents have been identified. In this study, we demonstrated that Nutlin-3 could abolish the down-regulation of E-cadherin induced by TGF-β1 in p53-deficient cancer cells. Further studies revealed that Nutlin-3 prohibited EMT by blocking the phosphorylation of Smad2/3, resulting in the decreased transcription of Snail/Slug. In addition, Nutlin-3 suppressed the motility of cancer cells, and potentiated the anti-proliferative activity of gefitinib and lapatinib. Collectively, Nutlin-3 could inhibit EMT and enhance the anti-cancer activity of EGFR inhibitors by interfering with the canonical TGF-β1-Smad-Snail/Slug axis, in a p53-independent manner.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Wu Y,Fu Y,Zheng L,Lin G,Ma J,Lou J,Zhu H,He Q,Yang B

doi

10.1016/j.canlet.2013.08.039

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

82-91

issue

1

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(13)00624-1

journal_volume

342

pub_type

杂志文章
  • Combined evaluation of dihydropyrimidine dehydrogenase and thymidine phosphorylate mRNA levels in tumor predicts the histopathological effect of 5-fluorouracil-based chemoradiotherapy.

    abstract::Recent clinical studies have indicated that intra-tumoral gene expression levels of 5-fluorouracil (5-FU) metabolism-related enzymes may predict the clinical response of several cancers to 5-FU-based chemotherapy. However, few studies examining oral squamous cell carcinomas (OSCCs) have been reported. In this study, w...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2008.09.010

    authors: Tateishi Y,Tatemoto Y,Ohno S,Morishita K,Ueta E,Yamamoto T

    更新日期:2009-02-18 00:00:00

  • Circulating RNA as a novel tumor marker: an in vitro study of the origins and characteristics of extracellular RNA.

    abstract::Many clinical studies have shown that circulating RNA rises in cancer patients, but little is known about the origins of abnormally elevated extracellular RNA (exRNA). We designed four different culture conditions: serum-deprived, hypoxia, low temperature and exposure to an anticancer drug to investigate the origins i...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2007.09.016

    authors: Zhou H,Xu W,Qian H,Yin Q,Zhu W,Yan Y

    更新日期:2008-01-18 00:00:00

  • MAGEA6 promotes human glioma cell survival via targeting AMPKα1.

    abstract::Melanoma antigen A6 (MAGEA6)/TRIM28 complex is a cancer-specific ubiquitin ligase, which degradates tumor suppressor protein AMP-activated protein kinase (AMPK). We show that MAGEA6 is uniquely expressed in human glioma tissues and cells, which is correlated with AMPKα1 downregulation. It is yet absent in normal brain...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2017.09.051

    authors: Pan SJ,Ren J,Jiang H,Liu W,Hu LY,Pan YX,Sun B,Sun QF,Bian LG

    更新日期:2018-01-01 00:00:00

  • Ellagic acid inhibits human pancreatic cancer growth in Balb c nude mice.

    abstract::Ellagic acid (EA) is a polyphenol found in several plants and fruits. The objectives of this study were to examine the molecular mechanisms by which EA inhibits pancreatic cancer growth in Balb C nude mice. PANC-1 cells were injected subcutaneously into Balb c nude mice, and tumor-bearing mice were treated with EA. Th...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2013.05.009

    authors: Zhao M,Tang SN,Marsh JL,Shankar S,Srivastava RK

    更新日期:2013-09-01 00:00:00

  • P5 HER2/neu-derived peptide conjugated to liposomes containing MPL adjuvant as an effective prophylactic vaccine formulation for breast cancer.

    abstract::Vaccines containing synthetic peptides derived from tumor-associated antigens (TAA) can elicit potent cytotoxic T lymphocyte (CTL) response if they are formulated in an optimal vaccine delivery system. The aim of this study was to develop a simple and effective lipid-based vaccine delivery system using P5 HER2/neu-der...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2014.09.016

    authors: Shariat S,Badiee A,Jalali SA,Mansourian M,Yazdani M,Mortazavi SA,Jaafari MR

    更新日期:2014-12-01 00:00:00

  • Adaptations of energy metabolism during cerebellar neurogenesis are co-opted in medulloblastoma.

    abstract::Recent studies show that metabolic patterns typical of cancer cells, including aerobic glycolysis and increased lipogenesis, are not unique to malignancy, but rather originate in physiologic development. In the postnatal brain, where sufficient oxygen for energy metabolism is scrupulously maintained, neural progenitor...

    journal_title:Cancer letters

    pub_type: 杂志文章,评审

    doi:10.1016/j.canlet.2014.02.017

    authors: Tech K,Deshmukh M,Gershon TR

    更新日期:2015-01-28 00:00:00

  • Nilotinib potentiates anticancer drug sensitivity in murine ABCB1-, ABCG2-, and ABCC10-multidrug resistance xenograft models.

    abstract::A panel of clinically used tyrosine kinase inhibitors were compared and nilotinib was found to most potently sensitize specific anticancer agents by blocking the functions of ABCB1/P-glycoprotein, ABCG2/BCRP and ABCC10/MRP7 transporters involved in multi-drug resistance. Nilotinib appreciably enhanced the antitumor re...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2012.10.001

    authors: Tiwari AK,Sodani K,Dai CL,Abuznait AH,Singh S,Xiao ZJ,Patel A,Talele TT,Fu L,Kaddoumi A,Gallo JM,Chen ZS

    更新日期:2013-01-28 00:00:00

  • N-Myc down-regulated gene 1 mediates proliferation, invasion, and apoptosis of hepatocellular carcinoma cells.

    abstract::The over-expression of N-myc down-regulated gene 1 (NDRG1) in hepatocellular carcinoma (HCC) was previously reported to correlate with vascular invasion and patient survival. Our current study aims to elucidate its functions in HCC. We found that it lacked the tumorigenic ability to promote soft agar colony formation ...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2007.12.010

    authors: Yan X,Chua MS,Sun H,So S

    更新日期:2008-04-08 00:00:00

  • Molecular co-expression of the c-Met oncogene and hepatocyte growth factor in primary colon cancer predicts tumor stage and clinical outcome.

    abstract:INTRODUCTION/HYPOTHESIS:Over-expression of the c-Met receptor tyrosine kinase has been described in a variety of cancers and implicated in tumor progression. Unlike some solid tumors, current evidence indicates that c-Met activation in colon cancer is unrelated to gene mutation, is ligand dependent, and occurs via a pa...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2006.07.007

    authors: Kammula US,Kuntz EJ,Francone TD,Zeng Z,Shia J,Landmann RG,Paty PB,Weiser MR

    更新日期:2007-04-18 00:00:00

  • Immunotherapy for pancreatic cancer: A long and hopeful journey.

    abstract::Multiple therapeutic strategies have been developed to treat pancreatic cancer. However, the outcomes of these approaches are disappointing. Due to deeper understandings of the pivotal roles of the immune system in pancreatic cancer tumorigenesis and progression, novel therapeutic strategies based on immune cells and ...

    journal_title:Cancer letters

    pub_type: 杂志文章,评审

    doi:10.1016/j.canlet.2018.03.040

    authors: Xu JW,Wang L,Cheng YG,Zhang GY,Hu SY,Zhou B,Zhan HX

    更新日期:2018-07-01 00:00:00

  • Prostate-specific membrane antigen-targeted photodynamic therapy induces rapid cytoskeletal disruption.

    abstract::Prostate-specific membrane antigen (PSMA), an established enzyme-biomarker for prostate cancer, has attracted considerable attention as a target for imaging and therapeutic applications. We aimed to determine the effects of PSMA-targeted photodynamic therapy (PDT) on cytoskeletal networks in prostate cancer cells. PSM...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2010.04.003

    authors: Liu T,Wu LY,Berkman CE

    更新日期:2010-10-01 00:00:00

  • Oncogene-induced regulation of microRNA expression: Implications for cancer initiation, progression and therapy.

    abstract::A plethora of tumours have characteristic oncogenic mutations which are the main causes of malignant transformation, exerting their effects through multiple signalling pathways. Downstream of such pathways, microRNAs are small non-coding RNAs that negatively regulate gene expression, assisting or antagonizing oncogeni...

    journal_title:Cancer letters

    pub_type: 杂志文章,评审

    doi:10.1016/j.canlet.2018.02.029

    authors: Paliouras AR,Monteverde T,Garofalo M

    更新日期:2018-05-01 00:00:00

  • Synergistic cytotoxic effect of human recombinant tumor necrosis factor alpha combined with dihydroambazone.

    abstract::Dihydroambazone (DHA) is a water-soluble derivative of the experimental anticancer drug ambazone. In vitro, a combination of DHA and human recombinant tumor necrosis factor alpha (TNF) exerted a strong synergism of cytotoxicity against both mouse melanoma B16K cells and the TNF-sensitive mouse fibroblast line L-M (S)....

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/0304-3835(90)90032-s

    authors: Baumgart J,Gase K,Schulze W,Suehnel J,Gutsche W,Behnke D

    更新日期:1990-11-05 00:00:00

  • Butein induces G(2)/M phase arrest and apoptosis in human hepatoma cancer cells through ROS generation.

    abstract::We investigated the molecular effects of 3,4,2',4'-tetrahydroxychalcone (butein) treatment in two human hepatoma cancer cell lines-HepG2 and Hep3B. Butein treatment inhibited cancer cell growth by inducing G(2)/M phase arrest and apoptosis. Butein-induced G(2)/M phase arrest was associated with increased ATM, Chk1, an...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2009.07.002

    authors: Moon DO,Kim MO,Choi YH,Hyun JW,Chang WY,Kim GY

    更新日期:2010-02-28 00:00:00

  • Carcinogen dose-dependent variation in the transgene mutation spectrum in urethane-induced lung tumors in transgenic mice carrying the human prototype c-Ha-ras gene.

    abstract::Urethane-induced lung tumors and their genetic changes were investigated in transgenic (Tg) mice carrying a human prototype c-Ha-ras gene (rasH2 mice). Male and female rasH2 mice and non-transgenic (non-Tg) littermates were injected intraperitoneally with 1000 mg/kg of urethane once or three times at 2-day intervals. ...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/s0304-3835(00)00372-4

    authors: Mori I,Yasuhara K,Hayashi SM,Nonoyama T,Nomura T,Mitsumori K

    更新日期:2000-05-29 00:00:00

  • G9a inhibition potentiates the anti-tumour activity of DNA double-strand break inducing agents by impairing DNA repair independent of p53 status.

    abstract::Cancer cells often exhibit altered epigenetic signatures that can misregulate genes involved in processes such as transcription, proliferation, apoptosis and DNA repair. As regulation of chromatin structure is crucial for DNA repair processes, and both DNA repair and epigenetic controls are deregulated in many cancers...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2016.07.009

    authors: Agarwal P,Jackson SP

    更新日期:2016-10-01 00:00:00

  • Influence of tocopherol on tumour cell oxygenation.

    abstract::Tocopherol, a well known tissue anti-oxidant, given before local X-ray irradiation of 2 transplantable rat tumours was previously found to increase significantly the effect of irradiation. In the present study tocopherol did not influence the development of tumour necroses during growth of a transplantable rat hepatom...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/s0304-3835(78)80037-8

    authors: Kågerud A,Klintenberg C,Lund N,Peterson HI

    更新日期:1978-10-01 00:00:00

  • Selective hyperexpression of c-jun oncoprotein by glass fiber- and silica-transformed BALB/c-3T3 cells.

    abstract::Mining and mineral processing are important industries in the United States. A large number of workers are potentially exposed to silica during mining and to glass fibers during manufacturing. There is a concern regarding lung cancer risk among workers exposed to silica and glass fibers. Our previous studies showed th...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/s0304-3835(96)04546-6

    authors: Gao H,Brick J,Ong S,Miller M,Whong WZ,Ong T

    更新日期:1997-01-15 00:00:00

  • Expression profiling identifies epoxy anthraquinone derivative as a DNA topoisomerase inhibitor.

    abstract::To discover novel drugs for neuroblastoma treatment, we have previously screened a panel of drugs and identified 30 active agents against neuroblastoma cells. Here we performed microarray gene expression analysis to monitor the impact of these agents on a neuroblastoma cell line and used the connectivity map (cMAP) to...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2010.01.004

    authors: Gheeya J,Johansson P,Chen QR,Dexheimer T,Metaferia B,Song YK,Wei JS,He J,Pommier Y,Khan J

    更新日期:2010-07-01 00:00:00

  • Deregulated c-myc expression is insufficient for emergence of the tumorigenic phenotype in malignancy-suppressed intratypic T-cell lymphoma hybrids: an in vitro model for multistep lymphomagenesis.

    abstract::The T-cell lymphoma cell line YACUT was fused with the Mls-1a antigen-responsive non-tumorigenic T-cell line G4 to construct growth-arrested hybrids which could be induced to proliferate in the presence of Mls-1a antigen. Prolonged growth of the hybrids by repeated antigenic stimulation resulted in the emergence of ce...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/0304-3835(96)04135-3

    authors: Kubota K,Tamauchi H,Nakazato K

    更新日期:1996-03-29 00:00:00

  • Combined effects of gender, skin type and polymorphic genes on clinical phenotype: use of rate of increase in numbers of basal cell carcinomas as a model system.

    abstract::Patients with a basal cell carcinomas (BCC) have an increased risk of further tumors. We studied the individual and combined impact of gender, skin type and allelic genes cytochrome P450 (CYP2D6), vitamin D receptor (VDR), tumor necrosis factor-alpha, TNF-alpha) on the rate of increase in BCC numbers after first prese...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/s0304-3835(02)00516-5

    authors: Ramachandran S,Fryer AA,Lovatt TJ,Smith AG,Lear JT,Jones PW,Strange RC

    更新日期:2003-01-28 00:00:00

  • Effects of capsaicin on liver microsomal metabolism of the tobacco-specific nitrosamine NNK.

    abstract::Chemically-induced mutagenesis and carcinogenesis is modulated by various plant products, some of which are present in the human diet. 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a potent carcinogen in tobacco and tobacco smoke, is activated by microsomal enzymes. In this study, we investigated the effects o...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/0304-3835(93)90206-o

    authors: Miller CH,Zhang Z,Hamilton SM,Teel RW

    更新日期:1993-11-30 00:00:00

  • In vivo efficacy of HAT therapy against transplantable murine myelomas resistant to purine analogs.

    abstract::The therapeutic efficacy of antineoplastic purine analogs can be jeopardized by the emergence of drug-resistant mutant subpopulations of tumor cells. To determine whether such mutant populations might be eradicable in vivo with the type of HAT combination (hypoxanthine + an antifolate + thymidine) known to be selectiv...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/0304-3835(86)90152-7

    authors: Moolten FL

    更新日期:1986-06-01 00:00:00

  • Phenotypic differentiation of human breast cancer cells by 1,3 cyclic propanediol phosphate.

    abstract::Breast cancer cells in their virulent undifferentiated state are characterized by lack of functional estrogen receptors (ER) and/or progesterone receptors (PR) as well as relatively low levels of other normal differentiation markers such as milk proteins and lipid droplets. To date, no method for in situ elevation of ...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/s0304-3835(03)00146-0

    authors: Adan Y,Goldman Y,Haimovitz R,Mammon K,Eilon T,Tal S,Tene A,Karmel Y,Shinitzky M

    更新日期:2003-05-08 00:00:00

  • Ritalin, Benzedrine and Dexedrine do not transform F 1706 rat cells.

    abstract::Ritalin (methylphenidate hydrochloride), Benzedrine (amphetamine sulfate), and Dexedrine (dextroamphetamine sulfate) were examined for oncogenicity using a serial line of Fischer rat embryo cells, which was previously shown to be a sensitive and accurate indicator of chemicals carcinogenic for rodents. At the concentr...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/s0304-3835(78)80061-5

    authors: Price PJ,Gregory EA,Skeen PC

    更新日期:1978-12-01 00:00:00

  • A combination of a DNA-chimera siRNA against PLK-1 and zoledronic acid suppresses the growth of malignant mesothelioma cells in vitro.

    abstract::Although novel agents effective against malignant mesothelioma (MM) have been developed, the prognosis of patients with MM is still poor. We generated a DNA-chimeric siRNA against polo-like kinase-1 (PLK-1), which was more stable in human serum than the non-chimeric siRNA. The chimeric PLK-1 siRNA inhibited MM cell pr...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2010.02.008

    authors: Kawata E,Ashihara E,Nakagawa Y,Kiuchi T,Ogura M,Yao H,Sakai K,Tanaka R,Nagao R,Yokota A,Takeuchi M,Kimura S,Hirai H,Maekawa T

    更新日期:2010-08-28 00:00:00

  • Embelin inhibits pancreatic cancer progression by directly inducing cancer cell apoptosis and indirectly restricting IL-6 associated inflammatory and immune suppressive cells.

    abstract::Pancreatic cancer is an aggressive malignancy and unresponsive to conventional chemotherapies. Here, the anti-inflammatory and anti-tumor effects of embelin on pancreatic cancer were investigated. Embelin significantly attenuated cells invasion, proliferation and induced apoptosis through inhibition of STAT3 and activ...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2014.08.011

    authors: Peng M,Huang B,Zhang Q,Fu S,Wang D,Cheng X,Wu X,Xue Z,Zhang L,Zhang D,Da Y,Dai Y,Yang Q,Yao Z,Qiao L,Zhang R

    更新日期:2014-11-28 00:00:00

  • APAF-1 signaling in human melanoma.

    abstract::Acquired resistance to mechanisms of programmed cell death is one of the hallmarks of cancer. Human melanoma, in advanced stage, is hardly curable, due to development of several strategies that impair apoptosis induced by the death receptor and the mitochondrial pathways of apoptosis. Among these apoptosis escape stra...

    journal_title:Cancer letters

    pub_type: 杂志文章,评审

    doi:10.1016/j.canlet.2005.06.034

    authors: Anichini A,Mortarini R,Sensi M,Zanon M

    更新日期:2006-07-18 00:00:00

  • Rectal epithelial proliferation characteristics of first degree relatives of sporadic colon cancer patients.

    abstract::Hyperproliferation of rectal epithelium is characteristic of families at high genetic risk for large bowel neoplasia, but has not been well-documented in families of sporadic colorectal cancer patients. This was studied in 119 such first degree relatives and 44 comparison subjects without this family history. All scre...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/0304-3835(90)90047-2

    authors: Rozen P,Fireman Z,Fine N,Chetrit A,Lubin F

    更新日期:1990-05-30 00:00:00

  • Trabectedin overcomes doxorubicin-resistance, counteracts tumor-immunosuppressive reprogramming of monocytes and decreases xenograft growth in Hodgkin lymphoma.

    abstract::Classical Hodgkin lymphoma (cHL) tumor cells are surrounded by a protective tumor microenvironment (TME). Trabectedin, an anticancer drug targeting both tumor cells and TME, demonstrated a potent antitumor activity against Hodgkin Reed Sternberg (HRS) cells. It was cytotoxic against cHL cell lines, including the doxor...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2020.12.015

    authors: Casagrande N,Borghese C,Favero A,Vicenzetto C,Aldinucci D

    更新日期:2021-03-01 00:00:00