c-Fos accelerates hepatocyte conversion to a fibroblastoid phenotype through ERK-mediated upregulation of paxillin-Serine178 phosphorylation.


:Transforming growth factor beta (TGF-beta) exerts an important role in the late steps of carcinogenesis by cooperating with Ras to induce cell motility and tumor invasion. The transcription complex AP-1 has been implicated in the regulation of genes involved in motility and invasion, by mechanisms not yet delineated. We utilized a model of immortalized human hepatocytes (IHH) overexpressing c-Fos (IHH-Fos) or not (IHH-C) to investigate the role of c-Fos on cell motility in response to a prolonged treatment with TGF-beta, EGF or a combination of both. Cotreatment with EGF and TGF-beta, but neither cytokine alone, induced the conversion of hepatocytes to a fibroblastoid phenotype and increased their motility in Boyden chambers. EGF/TGF-beta cotreatment induced a higher effect on ERK phosphorylation compared to TGF-beta treatment alone. It also induced an increase in total and phosphorylated Ser(178) paxillin, a protein previously implicated in cell motility. This response was inhibited by two specific MEK inhibitors, indicating the involvement of the ERK pathway in paxillin activation. Overexpression of c-Fos correlated with increased cell scattering and motility, higher levels of ERK activation and phospho Ser(178) paxillin, increased levels of EGF receptor (EGF-R) mRNA and higher EGF-R phosphorylation levels following EGF/TGF-beta cotreatment. Conversely, siRNA-mediated invalidation of c-Fos delayed the appearance of fibroblastoid cells, decreased EGF-R mRNA and downregulated ERK and Ser(178) paxillin phosphorylations, indicating that c-Fos activates hepatocyte motility through an EGF-R/ERK/paxillin pathway. Since c-Fos is frequently overexpressed in hepatocarcinomas, this newly identified mechanism might be involved in the progression of hepatic tumors in vivo.


Mol Carcinog


Molecular carcinogenesis


Güller MC,André J,Legrand A,Setterblad N,Mauviel A,Verrecchia F,Daniel F,Bernuau D




Has Abstract


2009-06-01 00:00:00












  • Rheb promotes cancer cell survival through p27Kip1-dependent activation of autophagy.

    abstract::We previously found that the small GTPase Rheb regulates the cell-cycle inhibitor p27KIP1 (p27) in colon cancer cells by a mTORC1-independent mechanism. However, the biological function of the Rheb/p27 axis in cancer cells remains unknown. Here, we show that siRNA-mediated depletion of Rheb decreases survival of human...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Campos T,Ziehe J,Palma M,Escobar D,Tapia JC,Pincheira R,Castro AF

    更新日期:2016-02-01 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


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

    更新日期:2013-09-01 00:00:00

  • Significance of FGF9 gene in resistance to anti-EGFR therapies targeting colorectal cancer: A subset of colorectal cancer patients with FGF9 upregulation may be resistant to anti-EGFR therapies.

    abstract::Although fibroblast growth factor (FGF) signals are strongly associated with malignancy, limited information is available regarding the role of the FGF9 signal in colorectal cancer (CRC). In this study, we investigated the frequency of FGF9 amplification in CRC clinical specimens and the association between the FGF9 g...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Mizukami T,Togashi Y,Naruki S,Banno E,Terashima M,de Velasco MA,Sakai K,Yoneshige A,Hayashi H,Fujita Y,Tomida S,Nakajima TE,Fujino T,Boku N,Ito A,Nakagawa K,Nishio K

    更新日期:2017-01-01 00:00:00

  • Increased manganese superoxide dismutase activity, protein, and mRNA levels and concurrent induction of tumor necrosis factor alpha in radiation-initiated Syrian hamster cells.

    abstract::The levels of the antioxidant enzyme manganese superoxide dismutase (Mn-SOD) are frequently decreased in tumor cells and increased in normal cells upon treatment with ionizing radiation. We studied Mn-SOD at different stages during the neoplastic conversion of radiation-initiated Syrian hamster embryo HDR-3 cells. Mn-...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Otero G,Avila MA,Emfietzoglou D,Clerch LB,Massaro D,Notario V

    更新日期:1996-12-01 00:00:00

  • Assessment of mutations in Ki-ras and p53 in colon cancers from azoxymethane- and dimethylhydrazine-treated rats.

    abstract::Mutations in the Ki-ras oncogene and the p53 tumor suppressor gene are known to occur at high frequencies in human colon cancers. We measured the frequency of mutations in these two genes in colon adenocarcinomas obtained from a widely used experimental model of human colon carcinogenesis: F344 rats treated with the c...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Erdman SH,Wu HD,Hixson LJ,Ahnen DJ,Gerner EW

    更新日期:1997-06-01 00:00:00

  • Overexpression of MDM-2 mRNA and mutation of the p53 tumor suppressor gene in bladder carcinoma cell lines.

    abstract::To investigate the importance of oncogenes and tumor suppressor genes in bladder carcinogenesis, we determined the status of the expression of the MDM-2 and p53 genes and genetic alterations in the p53 gene in five bladder carcinoma cell lines and one kidney urothelial carcinoma cell line. Overexpression of MDM-2 mRNA...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Cheng YT,Li YL,Wu JD,Long SB,Tzai TS,Tzeng CC,Lai MD

    更新日期:1995-07-01 00:00:00

  • Overexpression of Evi-1 oncoprotein represses TGF-β signaling in colorectal cancer.

    abstract::Human colorectal cancer (CRC) cells are resistant to the anti-proliferative effect of transforming growth factor-β (TGF-β), suggesting that disruption of TGF-β signaling plays an important role in colorectal carcinogenesis. Ecotropic virus integration site-1 (Evi-1) oncoprotein represses TGF-β signaling by interacting...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Deng X,Cao Y,Liu Y,Li F,Sambandam K,Rajaraman S,Perkins AS,Fields AP,Hellmich MR,Townsend CM Jr,Thompson EA,Ko TC

    更新日期:2013-04-01 00:00:00

  • Downregulation of STAT3/NF-κB potentiates gemcitabine activity in pancreatic cancer cells.

    abstract::There is an unmet need to develop new agents or strategies against therapy resistant pancreatic cancer (PanCA). Recent studies from our laboratory showed that STAT3 negatively regulates NF-κB and that inhibition of this crosstalk using Nexrutine® (Nx) reduces transcriptional activity of COX-2. Inhibition of these mole...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Gong J,Muñoz AR,Pingali S,Payton-Stewart F,Chan DE,Freeman JW,Ghosh R,Kumar AP

    更新日期:2017-02-01 00:00:00

  • Polyamines are oncometabolites that regulate the LIN28/let-7 pathway in colorectal cancer cells.

    abstract::Polyamine metabolism is a highly coordinated process that is essential for normal development and neoplastic growth in mammals. Although polyamine metabolism is a validated pathway for prevention of carcinogenesis, the mechanisms by which polyamines elicit their tumorigenic effects are poorly understood. In this study...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Paz EA,LaFleur B,Gerner EW

    更新日期:2014-02-01 00:00:00

  • Estrogen-induced cell transformation and DNA adduct formation in cultured Syrian hamster embryo cells.

    abstract::To study the possible involvement of DNA damage in cell transformation induced by estrogens, we examined whether DNA adduct formation is elicited in cultured Syrian hamster embryo (SHE) cells treated with estrogens and their derivatives by means of the 32P-postlabeling assay. Morphological transformation of the cells ...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Hayashi N,Hasegawa K,Komine A,Tanaka Y,McLachian JA,Barrett JC,Tsutsui T

    更新日期:1996-07-01 00:00:00

  • Intestinal microbiota: a potential diet-responsive prevention target in ApcMin mice.

    abstract::We previously reported that two dietary regimens, calorie restriction (CR) and a high olive oil-containing diet supplemented with a freeze-dried fruit and vegetable extract (OFV), reduced the development of intestinal adenomas in Apc(Min) mice by 57% and 33%, respectively, compared to control mice fed a defined diet a...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Mai V,Colbert LH,Perkins SN,Schatzkin A,Hursting SD

    更新日期:2007-01-01 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


    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

  • LW-213 induces G2/M cell cycle arrest through AKT/GSK3β/β-catenin signaling pathway in human breast cancer cells.

    abstract::LW-213 is a derivative of Wogonin and the anticancer activities of Wogonin have been reported. To study whether LW-213 inhibits cancer cells and explore a possible mechanism, we investigate the compound in several cancer cell lines. We found LW-213 arrests G2/M cycle in breast cancer cells by suppression of Akt/Gsk3β/...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Zhao L,Miao HC,Li WJ,Sun Y,Huang SL,Li ZY,Guo QL

    更新日期:2016-05-01 00:00:00

  • Aberrant expression and localization of connexin43 and connexin30 in a rat glioma cell line.

    abstract::Gap junctions are cellular structures which permit direct exchanges of small molecules from cytoplasm to cytoplasm in most of the cells of metazoan organisms. For four decades, it has been observed that the inhibition of this type of intercellular communication is often associated with tumorigenesis. The assumption th...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Mennecier G,Derangeon M,Coronas V,Hervé JC,Mesnil M

    更新日期:2008-05-01 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


    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

  • NATb/NAT1*4 promotes greater arylamine N-acetyltransferase 1 mediated DNA adducts and mutations than NATa/NAT1*4 following exposure to 4-aminobiphenyl.

    abstract::N-acetyltransferase 1 (NAT1) is a phase II metabolic enzyme responsible for the biotransformation of aromatic and heterocyclic amine carcinogens such as 4-aminobiphenyl (ABP). NAT1 catalyzes N-acetylation of arylamines as well as the O-acetylation of N-hydroxylated arylamines. O-acetylation leads to the formation of e...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Millner LM,Doll MA,Cai J,States JC,Hein DW

    更新日期:2012-08-01 00:00:00

  • Susceptibility of transgenic mice carrying human prototype c-Ha-ras gene in a short-term carcinogenicity study of vinyl carbamate and ras gene analyses of the induced tumors.

    abstract::To determine if hemizygous transgenic mice carrying the human c-Ha-ras gene (CB6F1-Tg Hras2 mice (Hras2 mice)) are susceptible to the carcinogenic potential of known murine carcinogens, male and female Hras2 mice and their non-transgenic CB6F1 littermates (non-Tg mice) were each given a single intraperitoneal injectio...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Mitsumori K,Wakana S,Yamamoto S,Kodama Y,Yasuhara K,Nomura T,Hayashi Y,Maronpot RR

    更新日期:1997-11-01 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


    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

  • Association of expression quantitative trait loci for long noncoding RNAs with lung cancer risk in Asians.

    abstract::Identification of long noncoding RNA (lncRNA) expression quantitative trait loci (lncR-eQTL) that associated with lung cancer can provide insights into regulatory mechanisms of lncRNA, and help reveal the role of lncRNA in lung cancer. A two-stage case-control design was implemented in this study. We first selected th...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Sun Q,Wang Y,Fan J,Li Z,Zhang J,Wang L,Fan X,Ji M,Zhu M,Dai J,Ma H,Jin G,Hu Z,Shen H

    更新日期:2019-07-01 00:00:00

  • AEBP1, a prognostic indicator, promotes colon adenocarcinoma cell growth and metastasis through the NF-κB pathway.

    abstract::The abnormal expression of adipocyte enhancer binding protein 1 (AEBP1) has been implicated in the carcinogenesis and progression of various types of human tumors. However, the role of AEBP1 in colon adenocarcinoma (COAD) remains largely unelucidated. In this study, we explored the clinical significance and biological...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Xing Y,Zhang Z,Chi F,Zhou Y,Ren S,Zhao Z,Zhu Y,Piao D

    更新日期:2019-10-01 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


    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

  • Uridine-cytidine kinase 2 upregulation predicts poor prognosis of hepatocellular carcinoma and is associated with cancer aggressiveness.

    abstract::Patients with advanced hepatocellular carcinoma (HCC) continue to have a dismal prognosis. Potential biomarkers to determine prognosis and select targeted therapies are urgently needed for patients with HCC. This study aimed to elucidate the role of UCK2 in HCC prognosis and tumor progression. We performed a screen of...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Huang S,Li J,Tam NL,Sun C,Hou Y,Hughes B,Wang Z,Zhou Q,He X,Wu L

    更新日期:2019-04-01 00:00:00

  • Effects of supplemental calcium and vitamin D on tight-junction proteins and mucin-12 expression in the normal rectal mucosa of colorectal adenoma patients.

    abstract::The physical gut barrier, comprised of a thick mucus layer and the epithelium, plays an important role in defense against microbes and foreign antigens. Calcium and vitamin D may be involved in maintaining the integrity of the intestinal mucosal barrier, the dysfunction of which may lead to endotoxemia and inflammatio...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章,多中心研究,随机对照试验


    authors: Mandle HB,Jahan FA,Bostick RM,Baron JA,Barry EL,Yacoub R,Merrill J,Rutherford RE,Seabrook ME,Fedirko V

    更新日期:2019-07-01 00:00:00

  • Benzo[a]pyrene diol-epoxide (B[a]PDE) upregulates COX-2 expression through MAPKs/AP-1 and IKKbeta/NF-kappaB in mouse epidermal Cl41 cells.

    abstract::Benzo[alpha]pyrene-7,8-diol-9,10-epoxide (B[a]PDE), the major metabolite of benzo[a]pyrene (B[a]P), shows an ultimate complete carcinogen in various animals and is a causative agent for human cancers. However, its effects on the activation of signal pathways and the expression of genes involved in its carcinogenic eff...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Ouyang W,Ma Q,Li J,Zhang D,Ding J,Huang Y,Xing MM,Huang C

    更新日期:2007-01-01 00:00:00

  • Alsterpaullone, a novel cyclin-dependent kinase inhibitor, induces apoptosis by activation of caspase-9 due to perturbation in mitochondrial membrane potential.

    abstract::The majority of human neoplasms have aberrations in the retinoblastoma pathway due to hyperactivation of cyclin-dependent kinases (CDK). Based on this observation, novel small molecules, such as flavopiridol and UCN-01, are being developed and are currently being tested in the clinic. Efforts to develop CDK modulators...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Lahusen T,De Siervi A,Kunick C,Senderowicz AM

    更新日期:2003-04-01 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


    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

  • Reduction in transforming growth factor-beta type II receptor in mouse lung carcinogenesis.

    abstract::Transforming growth factor-beta (TGF-beta) is a growth modulator that inhibits the proliferation of many epithelial cells through interaction with its receptors, the type I and type II receptors (TGF-beta RI and RII) by activating their serine/threonine kinase activities. Loss of growth inhibition by TGF-beta is thoug...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Jakowlew SB,Moody TW,You L,Mariano JM

    更新日期:1998-05-01 00:00:00

  • Wogonin suppresses human alveolar adenocarcinoma cell A549 migration in inflammatory microenvironment by modulating the IL-6/STAT3 signaling pathway.

    abstract::Increasing evidence from various clinical and experimental studies has demonstrated that the inflammatory microenvironment facilitates tumor metastasis. Clinically, it will be a promising choice to suppress tumor metastasis by targeting inflammatory microenvironment. Our previous studies have demonstrated that wogonin...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Zhao Y,Yao J,Wu XP,Zhao L,Zhou YX,Zhang Y,You QD,Guo QL,Lu N

    更新日期:2015-06-01 00:00:00

  • KIT polymorphisms were associated with the risk for head and neck squamous carcinoma in Chinese population.

    abstract::KITLG/KIT pathway plays a vital role in multiple types of human cancer including head and neck squamous cell carcinoma (HNSCC). Genetic variations in KITLG and KIT may affect the expression or function of these genes, thereby modifying cancer risk. In this study, we evaluated the association of KITLG and KIT polymorph...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Hang D,Yuan H,Liu L,Wang L,Miao L,Zhu M,Du J,Dai J,Hu Z,Chen N,Shen H,Ma H

    更新日期:2017-01-01 00:00:00

  • Expression of peptidylarginine deiminase type 4 (PAD4) in various tumors.

    abstract::Peptidylarginine deiminase type 4 (PAD4/PADI4) posttranslationally converts peptidylarginine to citrulline, in a process known as citrullination. Evidence suggests that PAD4 plays an essential role in pathogenesis of rheumatoid arthritis (RA). RA synovium has many features in common with tumor tissues, including abnor...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Chang X,Han J

    更新日期:2006-03-01 00:00:00