Modification of p27 with O-linked N-acetylglucosamine regulates cell proliferation in hepatocellular carcinoma.


:The tumor suppressor p27, which is a member of the Cip/Kip family of Cyclin-dependent kinase inhibitory proteins (CKIs), controls anti-proliferative events. The post-translational addition of O-GlcNAc to p27 occurs in HEK293T and HCC (hepatocellular carcinoma) cell lines, and we identified Ser2, Ser106, Ser110, Thr157, and Thr198 as the glycosylation sites of p27 based on the Q-TOF spectrum. Here, immunoprecipitation analysis showed that Ser2 was O-GlcNAcylated and that this modification was associated with the increased phosphorylation of p27 at Ser10, ultimately resulting in p27 accumulation in the cytoplasm and increased p27 ubiquitination. In addition, O-GlcNAcylation at Ser2 suppressed Cyclin/CDK complex-p27 interactions by promoting the nuclear export of p27, thus facilitating cell cycle progression. Cell proliferation was negatively regulated when Ser2 of p27 was replaced with Ala. Furthermore, western blot and immunohistochemical analyses of HCC tissues and their corresponding nontumorous tissues were performed, and we found that O-GlcNAcylated p27 correlated with cell proliferation in HCC. Together, our results indicate that the dynamic interplay between O-GlcNAcylation and p27 phosphorylation coordinates and regulates cell proliferation in hepatocellular carcinoma. © 2016 Wiley Periodicals, Inc.


Mol Carcinog


Molecular carcinogenesis


Qiu H,Liu F,Tao T,Zhang D,Liu X,Zhu G,Xu Z,Ni R,Shen A




Has Abstract


2017-01-01 00:00:00












  • Differential expression of Axl in hepatocellular carcinoma and correlation with tumor lymphatic metastasis.

    abstract::Protein kinases play important roles in tumor development and progression. A variety of members of the signal transduction enzymes serve as targets for therapeutic intervention in cancer. The dysregulation of Axl receptor and its ligand growth arrest-specific 6 (Gas6) is implicated in the pathogenesis of several cance...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: He L,Zhang J,Jiang L,Jin C,Zhao Y,Yang G,Jia L

    更新日期:2010-10-01 00:00:00

  • New genetic variations discovered in KRAS wild-type cetuximab resistant chinese colorectal cancer patients.

    abstract::To perform a comprehensive genomic analysis of colorectal cancer (CRC) tumor to detect genetic variants and identify novel resistant mutations associated with cetuximab-resistance in CRC patients. A retrospective study was performed using whole exome sequencing (WES) to identify common genetic factors from 22 cetuxima...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Jing C,Wang T,Ma R,Cao H,Wang Z,Liu S,Chen D,Zhang J,Wu Y,Zhang Y,Wu J,Feng J

    更新日期:2020-05-01 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

  • Dual use of hematopoietic and mesenchymal stem cells enhances engraftment and immune cell trafficking in an allogeneic humanized mouse model of head and neck cancer.

    abstract::In this report, we describe in detail the evolving procedures to optimize humanized mouse cohort generation, including optimal conditioning, choice of lineage for engraftment, threshold for successful engraftment, HNSCC tumor implantation, and immune and stroma cell analyses. We developed a dual infusion protocol of h...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Morton JJ,Keysar SB,Perrenoud L,Chimed TS,Reisinger J,Jackson B,Le PN,Nieto C,Gomez K,Miller B,Gao D,Somerset H,Wang XJ,Jimeno A

    更新日期:2018-11-01 00:00:00

  • Transactivating agonists of the EGF receptor require Tyr 845 phosphorylation for induction of DNA synthesis.

    abstract::Signaling networks play important roles in cancer progression. For example, overexpression of the epidermal growth factor receptor (EGFR) is a poor prognostic indicator in multiple tumor types. Recent studies have postulated that the EGFR functions as a central conduit for signaling by different classes of cell surfac...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Boerner JL,Biscardi JS,Silva CM,Parsons SJ

    更新日期:2005-12-01 00:00:00

  • Further assessment of exome-wide UVR footprints in melanoma and their possible relevance.

    abstract::C>T substitutions at dipyrimidine sites dominate the melanoma genome. We recently analyzed the exomes of spontaneous and neonatal UVR-induced murine melanomas, noting a dramatic change in the genomic footprint at C>T substitutions in the latter. Here we re-analyzed published exome-wide footprints in human melanomas st...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Mukhopadhyay P,Roberts JA,Walker GJ

    更新日期:2017-06-01 00:00:00

  • Polymorphisms in GSTM1 and XPD genes predict clinical outcome in advanced oral cancer patients treated with postoperative radiotherapy.

    abstract::Polymorphisms in metabolic and DNA repair genes may alter protein function, consequently affecting patients' response to chemo/radiotherapy. We retrospectively assessed whether polymorphisms of glutathione-S-transferase genes GSTM1 (deletion), GSTT1 (deletion), GSTP1 (Ile105Val, rs1695), and DNA repair genes hOGG1 (Se...

    journal_title:Molecular carcinogenesis

    pub_type: 临床试验,杂志文章


    authors: Mahimkar MB,Samant TA,Kannan S,Tulsulkar J,Pai PS,Anantharaman D

    更新日期:2012-10-01 00:00:00

  • Mango polyphenolics reduce inflammation in intestinal colitis-involvement of the miR-126/PI3K/AKT/mTOR axis in vitro and in vivo.

    abstract::This study sought to elucidate the mechanisms underlying the anti-inflammatory effect of mango (Mangifera Indica L.) polyphenolics containing gallic acid and gallotanins, and the role of the miR-126/PI3K/AKT/mTOR signaling axis in vitro and in vivo. Polyphenolics extracted from mango (var. Keitt) were investigated in ...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Kim H,Banerjee N,Barnes RC,Pfent CM,Talcott ST,Dashwood RH,Mertens-Talcott SU

    更新日期:2017-01-01 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

  • Gene expression profiling as a tool for basic analysis and clinical application of human cancer.

    abstract::The sequentiation of the human genome, together with the development of high throughput technologies, particularly gene-expression profiling, is giving us the opportunity to describe biological features in a quantitative manner. Here we review the use of global gene expression analyses in cancer research. Microarray a...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: García-Escudero R,Paramio JM

    更新日期:2008-08-01 00:00:00

  • Antitumor Effect of Periplocin in TRAIL-Resistant gastric cancer cells via upregulation of death receptor through activating ERK1/2-EGR1 pathway.

    abstract::Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a member of the tumor necrosis factor family, induces apoptosis in a variety of cancer cells. However, gastric cancer (GC) cells are insensitive to TRAIL usually. In the previous study, we showed that Periplocin could induce apoptosis in GC cells via the...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Zhao LM,Li L,Huang Y,Han LJ,Li D,Huo BJ,Dai SL,Xu LY,Zhan Q,Shan BE

    更新日期:2019-06-01 00:00:00

  • Cinnamon extract reduces VEGF expression via suppressing HIF-1α gene expression and inhibits tumor growth in mice.

    abstract::Although many anti-VEGF agents are available for cancer treatment, side effects of these agents limit their application for cancer treatment and prevention. Here we studied the potential use of a diet-based agent as an inhibitor for VEGF production. Using a VEGF reporter assay, our data showed that an extract from cin...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Zhang K,Han ES,Dellinger TH,Lu J,Nam S,Anderson RA,Yim JH,Wen W

    更新日期:2017-02-01 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

  • Inhibition of proliferation and expression of T1 and cyclin D1 genes by thyroid hormone in mammary epithelial cells.

    abstract::The relationship between thyroid hormone (triiodothyronine, T(3)) and breast cancer is unclear. We studied the effect of the c-erbA/TR alpha proto-oncogene encoding a functional T(3) receptor (TR alpha 1), of its ligand T(3), and of its retroviral, mutated counterpart, the v-erbA oncogene, on the proliferation capacit...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: González-Sancho JM,Figueroa A,López-Barahona M,López E,Beug H,Muñoz A

    更新日期:2002-05-01 00:00:00

  • Betulinic acid suppresses constitutive and TNFalpha-induced NF-kappaB activation and induces apoptosis in human prostate carcinoma PC-3 cells.

    abstract::Development of chemoresistance in androgen-refractory prostate cancer cells is partly due to constitutive activation of Rel/NF-kappaB transcription factors that regulate several cell survival and anti-apoptotic genes. In this study we examined whether betulinic acid (BetA), a pentacyclic triterpene from the bark of wh...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Rabi T,Shukla S,Gupta S

    更新日期:2008-12-01 00:00:00

  • LncRNA DANCR promotes tumor growth and angiogenesis in ovarian cancer through direct targeting of miR-145.

    abstract::Differentiation antagonizing non-protein coding RNA (DANCR) is a newly identified oncogenic long noncoding RNA found in various cancers. However, the functional role of DANCR in tumor angiogenesis and the underlying mechanisms are still unclear. The expression of DANCR was determined in ovarian malignant tissues and c...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Lin X,Yang F,Qi X,Li Q,Wang D,Yi T,Yin R,Zhao X,Zhong X,Bian C

    更新日期:2019-12-01 00:00:00

  • miR-148a dependent apoptosis of bladder cancer cells is mediated in part by the epigenetic modifier DNMT1.

    abstract::Urothelial cell carcinoma of the bladder (UCCB) is the most common form of bladder cancer and it is estimated that ~15,000 people in the United States succumbed to this disease in 2013. Bladder cancer treatment options are limited and research to understand the molecular mechanisms of this disease is needed to design ...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Lombard AP,Mooso BA,Libertini SJ,Lim RM,Nakagawa RM,Vidallo KD,Costanzo NC,Ghosh PM,Mudryj M

    更新日期:2016-05-01 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

  • 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


    authors: Murakami A,Tanaka H

    更新日期:1991-01-01 00:00:00

  • Evidence that mutational activation of the ras genes may not be involved in aflatoxin B(1)-induced human hepatocarcinogenesis, based on sequence analysis of the ras and p53 genes.

    abstract::Exposure to aflatoxin B(1) (AFB(1)) is one of the risk factors for developing hepatoma. In rats, activation of the ras gene is a prevalent event in AFB(1)-induced hepatocarcinogenesis. It is not clear whether a similar event occurs in humans. By analysis of codon 249 of the p53 gene, six of 36 human hepatoma samples w...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Chao HK,Tsai TF,Lin CS,Su TS

    更新日期:1999-10-01 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


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

    更新日期:1994-02-01 00:00:00

  • The role of the hypoxia-Nrp-1 axis in the activation of M2-like tumor-associated macrophages in the tumor microenvironment of cervical cancer.

    abstract::To explore the mechanisms through which hypoxic tumor microenvironment (TME) modulates the transition of tumor-associated macrophages (TAMs). The migration ability of RAW264.7 macrophages was determined by transwell assay. Flow cytometric, western blot and immunofluorescence analyses of CD206 further validated the M2 ...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Chen XJ,Wu S,Yan RM,Fan LS,Yu L,Zhang YM,Wei WF,Zhou CF,Wu XG,Zhong M,Yu YH,Liang L,Wang W

    更新日期:2019-03-01 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


    authors: Kumar AP,Garcia GE,Slaga TJ

    更新日期:2001-07-01 00:00:00

  • Cdkn2a encodes functional variation of p16INK4a but not p19ARF, which confers selection in mouse lung tumorigenesis.

    abstract::The cyclin-dependent kinase inhibitor 2a (Cdkn2a) locus encodes two distinct tumor suppressors, p16INK4a and p19ARF, whose functions interrelate in the regulation of cell proliferation as key components of the retinoblastoma and p53 pathways, respectively. In many types of cancer, alterations of Cdkn2a abrogate the fu...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Herzog CR,Noh S,Lantry LE,Guan KL,You M

    更新日期:1999-06-01 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


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

    更新日期:1995-11-01 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

  • Post-transcriptional up-regulation of miR-21 by type I collagen.

    abstract::Composition of extracellular matrix (ECM) is crucial to the establishment and maintenance of epithelial apical-basolateral polarity. Increased ECM rigidity caused by deposition of fibrillar collagen, for example, collagen type I (Col-1), promotes loss of epithelial polarity and tumor progression. microRNAs are small n...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Li C,Nguyen HT,Zhuang Y,Lin Y,Flemington EK,Guo W,Guenther J,Burow ME,Morris GF,Sullivan D,Shan B

    更新日期:2011-07-01 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


    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

  • Betulin induces mitochondrial cytochrome c release associated apoptosis in human cancer cells.

    abstract::We examined whether betulin, a naturally abundant compound, has anticancer functions in human cancer cells. The results showed that betulin significantly inhibited cell viability in cervix carcinoma HeLa cells, hepatoma HepG2 cells, lung adenocarcinoma A549 cells, and breast cancer MCF-7 cells with IC(50) values rangi...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Li Y,He K,Huang Y,Zheng D,Gao C,Cui L,Jin YH

    更新日期:2010-07-01 00:00:00

  • Gene expression changes associated with chemically induced rat mammary carcinogenesis.

    abstract::Experimentally induced models of breast carcinogenesis in the rat are widely used for studying the biology of breast cancer and for developing and evaluating cancer prevention and control strategies. However, very little is known about gene expression changes that are associated with experimentally induced mammary car...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Lu J,Pei H,Kaeck M,Thompson HJ

    更新日期:1997-10-01 00:00:00