Holliday junction recognition protein promotes pancreatic cancer growth and metastasis via modulation of the MDM2/p53 signaling.

Abstract:

:Holliday junction recognition protein (HJURP) refers to a histone H3 chaperone that has been implicated in different kinds of malignancies. Yet, its character in pancreatic cancer remains unclear. The expression of HJURP was assessed in PDAC tissues by RT-qPCR, immunoblotting, and immunohistochemistry. HJURP-deficient or overexpressed PDAC cell lines were constructed, using shRNA or plasmids with HJURP insert. MTT, sphere formation assay, migration, and invasion assays were performed to evaluate the viability, proliferation, migration, and invasion of PDAC cells. We used xenograft mice models to assess the tumor growth and metastasis in vivo. RNA-seq was applicated in search of the potential downstream target of HJURP in PDAC and subsequent verification were fulfilled via multiple assays, including immunofluorescence. Additionally, chromatin immunoprecipitation and luciferase reporter assay were conducted to explore the potential regulation of MDM2 expression by HJURP through H3K4me2. In this current research, we found that the expression of HJURP in PDAC cells and tissue was significantly higher than those of adjacent normal tissue, and high HJURP expression predicted poor survival. HJURP significantly promoted the viability, sphere formation, migration, and invasion of PDAC cells in vitro, HJURP also facilitated tumor growth and metastasis in vivo. Mechanically, MDM2/p53 axis is critical for HJURP-mediated malignant behaviors in PDAC, and HJURP regulates MDM2 expression through H3K4me2. HJURP could serve as a promising biomarker, and target for PDAC prognosis and treatment.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Wang CJ,Li X,Shi P,Ding HY,Liu YP,Li T,Lin PP,Wang YS,Zhang GQ,Cao Y

doi

10.1038/s41419-020-2595-9

subject

Has Abstract

pub_date

2020-05-21 00:00:00

pages

386

issue

5

issn

2041-4889

pii

10.1038/s41419-020-2595-9

journal_volume

11

pub_type

杂志文章
  • Neurogenin 3+ cells contribute to β-cell neogenesis and proliferation in injured adult mouse pancreas.

    abstract::We previously showed that injury by partial duct ligation (PDL) in adult mouse pancreas activates Neurogenin 3 (Ngn3)(+) progenitor cells that can differentiate to β cells ex vivo. Here we evaluate the role of Ngn3(+) cells in β cell expansion in situ. PDL not only induced doubling of the β cell volume but also increa...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2013.52

    authors: Van de Casteele M,Leuckx G,Baeyens L,Cai Y,Yuchi Y,Coppens V,De Groef S,Eriksson M,Svensson C,Ahlgren U,Ahnfelt-Rønne J,Madsen OD,Waisman A,Dor Y,Jensen JN,Heimberg H

    更新日期:2013-03-07 00:00:00

  • From computational modelling of the intrinsic apoptosis pathway to a systems-based analysis of chemotherapy resistance: achievements, perspectives and challenges in systems medicine.

    abstract::Our understanding of the mitochondrial or intrinsic apoptosis pathway and its role in chemotherapy resistance has increased significantly in recent years by a combination of experimental studies and mathematical modelling. This combined approach enhanced the quantitative and kinetic understanding of apoptosis signal t...

    journal_title:Cell death & disease

    pub_type: 杂志文章,评审

    doi:10.1038/cddis.2014.36

    authors: Würstle ML,Zink E,Prehn JH,Rehm M

    更新日期:2014-05-29 00:00:00

  • Author Correction: Autophagic degradation of caveolin-1 promotes liver sinusoidal endothelial cells defenestration.

    abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    journal_title:Cell death & disease

    pub_type: 已发布勘误

    doi:10.1038/s41419-019-1722-y

    authors: Luo X,Wang D,Zhu X,Wang G,You Y,Ning Z,Li Y,Jin S,Huang Y,Hu Y,Chen T,Meng Y,Li X

    更新日期:2019-06-17 00:00:00

  • Inhibitor of apoptosis protein expression in glioblastomas and their in vitro and in vivo targeting by SMAC mimetic GDC-0152.

    abstract::Glioblastomas (GBMs) are the most aggressive primary brain tumors in adult and remain a therapeutic challenge. Targeting key apoptosis regulators with the ultimate aim to restore apoptosis in tumor cells could be an interesting therapeutic strategy. The inhibitors of apoptosis proteins (IAPs) are regulators of cell de...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2016.214

    authors: Tchoghandjian A,Soubéran A,Tabouret E,Colin C,Denicolaï E,Jiguet-Jiglaire C,El-Battari A,Villard C,Baeza-Kallee N,Figarella-Branger D

    更新日期:2016-08-04 00:00:00

  • Novel osmotin attenuates glutamate-induced synaptic dysfunction and neurodegeneration via the JNK/PI3K/Akt pathway in postnatal rat brain.

    abstract::The glutamate-induced excitotoxicity pathway has been reported in several neurodegenerative diseases. Molecules that inhibit the release of glutamate or cause the overactivation of glutamate receptors can minimize neuronal cell death in these diseases. Osmotin, a homolog of mammalian adiponectin, is a plant protein fr...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2013.538

    authors: Shah SA,Lee HY,Bressan RA,Yun DJ,Kim MO

    更新日期:2014-01-30 00:00:00

  • EphB3 receptors function as dependence receptors to mediate oligodendrocyte cell death following contusive spinal cord injury.

    abstract::We demonstrate that EphB3 receptors mediate oligodendrocyte (OL) cell death in the injured spinal cord through dependence receptor mechanism. OLs in the adult spinal cord express EphB3 as well as other members of the Eph receptor family. Spinal cord injury (SCI) is associated with tissue damage, cellular loss and dist...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2015.262

    authors: Tsenkina Y,Ricard J,Runko E,Quiala-Acosta MM,Mier J,Liebl DJ

    更新日期:2015-10-15 00:00:00

  • O6-methylguanine DNA methyltransferase as a promising target for the treatment of temozolomide-resistant gliomas.

    abstract::Temozolomide (TMZ) is an alkylating agent currently used as first-line therapy for gliomas treatment due to its DNA-damaging effect. However, drug resistance occurs, preventing multi-cycle use of this chemotherapeutic agent. One of the major mechanisms of cancer drug resistance is enhanced activity of a DNA repair enz...

    journal_title:Cell death & disease

    pub_type: 杂志文章,评审

    doi:10.1038/cddis.2013.388

    authors: Fan CH,Liu WL,Cao H,Wen C,Chen L,Jiang G

    更新日期:2013-10-24 00:00:00

  • IL-6 potentiates BMP-2-induced osteogenesis and adipogenesis via two different BMPR1A-mediated pathways.

    abstract::Recombinant human bone morphogenetic protein-2 (rhBMP-2) is widely used in the clinic for bone defect reconstruction because of its powerful osteoinductive capacity. However, commercially available rhBMP-2 requires a high concentration in the clinical setting for consistent bone formation. A high dose of rhBMP-2 induc...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-017-0126-0

    authors: Huang RL,Sun Y,Ho CK,Liu K,Tang QQ,Xie Y,Li Q

    更新日期:2018-02-02 00:00:00

  • Correction: Salvador-Warts-Hippo pathway regulates sensory organ development via caspase-dependent nonapoptotic signaling.

    abstract::Following publication of this article, it was brought to our attention that there was a typo in the References (reference number 43) whereby the first author's name was misspelled. The correct citation is provided below. We apologize for the inconvenience. ...

    journal_title:Cell death & disease

    pub_type: 已发布勘误

    doi:10.1038/s41419-019-2029-8

    authors: Wang LH,Baker NE

    更新日期:2019-10-22 00:00:00

  • Annonacin promotes selective cancer cell death via NKA-dependent and SERCA-dependent pathways.

    abstract::In the healthcare sector, phytocompounds are known to be beneficial by contributing or alleviating a variety of diseases. Studies have demonstrated the progressive effects of phytocompounds on immune-related diseases and to exhibit anticancer effects. Graviola tree is an evergreen tree with its extracts (leafs and see...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0772-x

    authors: Yiallouris A,Patrikios I,Johnson EO,Sereti E,Dimas K,De Ford C,Fedosova NU,Graier WF,Sokratous K,Kyriakou K,Stephanou A

    更新日期:2018-07-09 00:00:00

  • Metabolic and molecular insights into an essential role of nicotinamide phosphoribosyltransferase.

    abstract::Nicotinamide phosphoribosyltransferase (NAMPT) is a pleiotropic protein implicated in the pathogenesis of acute respiratory distress syndrome, aging, cancer, coronary heart diseases, diabetes, nonalcoholic fatty liver disease, obesity, rheumatoid arthritis, and sepsis. However, the underlying molecular mechanisms of N...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2017.132

    authors: Zhang LQ,Van Haandel L,Xiong M,Huang P,Heruth DP,Bi C,Gaedigk R,Jiang X,Li DY,Wyckoff G,Grigoryev DN,Gao L,Li L,Wu M,Leeder JS,Ye SQ

    更新日期:2017-03-23 00:00:00

  • The thiosemicarbazone Me2NNMe2 induces paraptosis by disrupting the ER thiol redox homeostasis based on protein disulfide isomerase inhibition.

    abstract::Due to their high biological activity, thiosemicarbazones have been developed for treatment of diverse diseases, including cancer, resulting in multiple clinical trials especially of the lead compound Triapine. During the last years, a novel subclass of anticancer thiosemicarbazones has attracted substantial interest ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-1102-z

    authors: Hager S,Korbula K,Bielec B,Grusch M,Pirker C,Schosserer M,Liendl L,Lang M,Grillari J,Nowikovsky K,Pape VFS,Mohr T,Szakács G,Keppler BK,Berger W,Kowol CR,Heffeter P

    更新日期:2018-10-15 00:00:00

  • Chloride channels are necessary for full platelet phosphatidylserine exposure and procoagulant activity.

    abstract::Platelets enhance thrombin generation at sites of vascular injury by exposing phosphatidylserine during necrosis-like cell death. Anoctamin 6 (Ano6) is required for Ca(2+)-dependent phosphatidylserine exposure and is defective in patients with Scott syndrome, a rare bleeding disorder. Ano6 may also form Cl(-) channels...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2013.495

    authors: Harper MT,Poole AW

    更新日期:2013-12-19 00:00:00

  • Sirt3 suppresses calcium oxalate-induced renal tubular epithelial cell injury via modification of FoxO3a-mediated autophagy.

    abstract::High oxalic acid and calcium oxalate (CaOx)-induced renal tubular epithelial cell (TEC) injury plays a key role in nephrolithiasis. However, the mechanism remains unknown. Gene array analysis of the mice nephrolithiasis model indicated significant downregulation of sirtuin 3 (Sirt3) and activation of mitogen-activated...

    journal_title:Cell death & disease

    pub_type: 杂志文章,收录出版

    doi:10.1038/s41419-018-1169-6

    authors: Peng Y,Yang C,Shi X,Li L,Dong H,Liu C,Fang Z,Wang Z,Ming S,Liu M,Xie B,Gao X,Sun Y

    更新日期:2019-01-15 00:00:00

  • Long non-coding RNA Myd88 promotes growth and metastasis in hepatocellular carcinoma via regulating Myd88 expression through H3K27 modification.

    abstract::Enhanced Myd88 expression has been found in various parenchymal tumors especially in hepatocellular carcinoma with little mechanism of its upregulation known. A lot of long non-coding RNAs are reported to regulate the protein-coding genes which have location association through various mechanisms. In our study we conf...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2017.519

    authors: Xu X,Yin Y,Tang J,Xie Y,Han Z,Zhang X,Liu Q,Qin X,Huang X,Sun B

    更新日期:2017-10-12 00:00:00

  • Inhibition of human mitochondrial peptide deformylase causes apoptosis in c-myc-overexpressing hematopoietic cancers.

    abstract::Inhibition of human mitochondrial peptide deformylase (HsPDF) depolarizes the mitochondrial membrane, reduces mitochondrial protein translation and causes apoptosis in Burkitt's lymphoma. We showed that HsPDF mRNA and protein levels were overexpressed in cancer cells and primary acute myeloid leukemia samples. Myc reg...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2014.112

    authors: Sheth A,Escobar-Alvarez S,Gardner J,Ran L,Heaney ML,Scheinberg DA

    更新日期:2014-03-27 00:00:00

  • Ex vivo culture of intestinal crypt organoids as a model system for assessing cell death induction in intestinal epithelial cells and enteropathy.

    abstract::Intestinal epithelial cells (IECs) not only have a critical function in the absorption of nutrients, but also act as a physical barrier between our body and the outside world. Damage and death of the epithelial cells lead to the breakdown of this barrier function and inflammation due to access of the immune system to ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2014.183

    authors: Grabinger T,Luks L,Kostadinova F,Zimberlin C,Medema JP,Leist M,Brunner T

    更新日期:2014-05-15 00:00:00

  • Identification of ML-9 as a lysosomotropic agent targeting autophagy and cell death.

    abstract::The growing number of studies suggested that inhibition of autophagy enhances the efficacy of Akt kinase inhibitors in cancer therapy. Here, we provide evidence that ML-9, a widely used inhibitor of Akt kinase, myosin light-chain kinase (MLCK) and stromal interaction molecule 1 (STIM1), represents the 'two-in-one' com...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2014.156

    authors: Kondratskyi A,Yassine M,Slomianny C,Kondratska K,Gordienko D,Dewailly E,Lehen'kyi V,Skryma R,Prevarskaya N

    更新日期:2014-04-24 00:00:00

  • CD10-/ALDH- cells are the sole cisplatin-resistant component of a novel ovarian cancer stem cell hierarchy.

    abstract::It is long established that tumour-initiating cancer stem cells (CSCs) possess chemoresistant properties. However, little is known of the mechanisms involved, particularly with respect to the organisation of CSCs as stem-progenitor-differentiated cell hierarchies. Here we aimed to elucidate the relationship between CS...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2017.379

    authors: Ffrench B,Gasch C,Hokamp K,Spillane C,Blackshields G,Mahgoub TM,Bates M,Kehoe L,Mooney A,Doyle R,Doyle B,O'Donnell D,Gleeson N,Hennessy BT,Stordal B,O'Riain C,Lambkin H,O'Toole S,O'Leary JJ,Gallagher MF

    更新日期:2017-10-19 00:00:00

  • Inhibitor of apoptosis proteins are required for effective fusion of autophagosomes with lysosomes.

    abstract::Inhibitor of Apoptosis Proteins act as E3 ubiquitin ligases to regulate NF-κB signalling from multiple pattern recognition receptors including NOD2, as well as TNF Receptor Superfamily members. Loss of XIAP in humans causes X-linked Lymphoproliferative disease type 2 (XLP-2) and is often associated with Crohn's diseas...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0508-y

    authors: Gradzka S,Thomas OS,Kretz O,Haimovici A,Vasilikos L,Wong WW,Häcker G,Gentle IE

    更新日期:2018-05-01 00:00:00

  • HCC-derived exosomes elicit HCC progression and recurrence by epithelial-mesenchymal transition through MAPK/ERK signalling pathway.

    abstract::Liver cancer is the second most common cause of cancer-related death worldwide. Approximately 70-90% of primary liver cancers are hepatocellular carcinoma (HCC). Currently, HCC patient prognosis is unsatisfactory due to high metastasis and/or post-surgical recurrence rates. Therefore, new therapeutic methods for inhib...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0534-9

    authors: Chen L,Guo P,He Y,Chen Z,Chen L,Luo Y,Qi L,Liu Y,Wu Q,Cui Y,Fang F,Zhang X,Song T,Guo H

    更新日期:2018-05-01 00:00:00

  • METTL3 regulates WTAP protein homeostasis.

    abstract::The Wilms tumor 1 (WT1)-associated protein (WTAP) is upregulated in many tumors, including, acute myeloid leukemia (AML), where it plays an oncogenic role by interacting with different proteins involved in RNA processing and cell proliferation. In addition, WTAP is also a regulator of the nuclear complex required for ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0843-z

    authors: Sorci M,Ianniello Z,Cruciani S,Larivera S,Ginistrelli LC,Capuano E,Marchioni M,Fazi F,Fatica A

    更新日期:2018-07-23 00:00:00

  • Mutations in the coat complex II component SEC23B promote colorectal cancer metastasis.

    abstract::Metastasis is the leading cause of death for colorectal cancer (CRC). However, the protein transport process involved in CRC metastasis remains unclear. In this report, we use whole-exome sequencing and bioinformatics analysis to identify somatic mutations in CRC samples and found mutations of the protein transport ge...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-2358-7

    authors: Yang C,Chen N,Li X,Lu D,Hou Z,Li Y,Jin Y,Gu J,Yin Y

    更新日期:2020-03-02 00:00:00

  • LINC81507 act as a competing endogenous RNA of miR-199b-5p to facilitate NSCLC proliferation and metastasis via regulating the CAV1/STAT3 pathway.

    abstract::Lung cancer is the leading cause of cancer-related mortality worldwide. Recently, accumulating data indicate that long noncoding RNAs (LncRNAs) function as novel crucial regulators of diverse biological processes, including proliferation and metastasis, in tumorigenesis. Lnc NONHSAT081507.1 (LINC81507) is associated w...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1740-9

    authors: Peng W,He D,Shan B,Wang J,Shi W,Zhao W,Peng Z,Luo Q,Duan M,Li B,Cheng Y,Dong Y,Tang F,Zhang C,Duan C

    更新日期:2019-07-11 00:00:00

  • Correction: Inhibition of IRE1α RNase activity reduces NLRP3 inflammasome assembly and processing of pro-IL1β.

    abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    journal_title:Cell death & disease

    pub_type: 已发布勘误

    doi:10.1038/s41419-019-2189-6

    authors: Talty A,Deegan S,Ljujic M,Mnich K,Naicker SD,Quandt D,Zeng Q,Patterson JB,Gorman AM,Griffin MD,Samali A,Logue SE

    更新日期:2020-01-06 00:00:00

  • MET/SMAD3/SNAIL circuit mediated by miR-323a-3p is involved in regulating epithelial-mesenchymal transition progression in bladder cancer.

    abstract::Bladder cancer (BCa) is the one of the most common cancers with high incidence, occurrence and low 5-year survival rate. Emerging evidence indicates that DLK1-DIO3 genomic region especially the miRNA cluster in this region is involved in several pathologic processes and various cancers, and miR-323a-3p is a member of ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2017.331

    authors: Li J,Xu X,Meng S,Liang Z,Wang X,Xu M,Wang S,Li S,Zhu Y,Xie B,Lin Y,Zheng X,Liu B,Xie L

    更新日期:2017-08-24 00:00:00

  • PKC signaling prevents irradiation-induced apoptosis of primary human fibroblasts.

    abstract::Primary cells respond to irradiation by activation of the DNA damage response and cell cycle arrest, which eventually leads to senescence or apoptosis. It is not clear in detail which signaling pathways or networks regulate the induction of either apoptosis or senescence. Primary human fibroblasts are able to withstan...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2013.15

    authors: Bluwstein A,Kumar N,Léger K,Traenkle J,Oostrum Jv,Rehrauer H,Baudis M,Hottiger MO

    更新日期:2013-02-14 00:00:00

  • TCF3, a novel positive regulator of osteogenesis, plays a crucial role in miR-17 modulating the diverse effect of canonical Wnt signaling in different microenvironments.

    abstract::Wnt signaling pathways are a highly conserved pathway, which plays an important role from the embryonic development to bone formation. The effect of Wnt pathway on osteogenesis relies on their cellular environment and the expression of target genes. However, the molecular mechanism of that remains unclear. On the basi...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2013.65

    authors: Liu W,Liu Y,Guo T,Hu C,Luo H,Zhang L,Shi S,Cai T,Ding Y,Jin Y

    更新日期:2013-03-14 00:00:00

  • Association of p21 with NF-YA suppresses the expression of Polo-like kinase 1 and prevents mitotic death in response to DNA damage.

    abstract::Polo-like kinase 1 (PLK1) is an important mitotic kinase and its expression is tightly regulated in the cell cycle and in the DNA damage response. PLK1 expression is previously shown to be suppressed by p53 and/or p21. Here, we demonstrate that the CCAAT box in the PLK1 promoter is pivotal for p53/p21-mediated PLK1 re...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2013.527

    authors: Lin YC,Chen YN,Lin KF,Wang FF,Chou TY,Chen MY

    更新日期:2014-01-09 00:00:00

  • Human colorectal cancer-derived mesenchymal stem cells promote colorectal cancer progression through IL-6/JAK2/STAT3 signaling.

    abstract::Mesenchymal stem cells (MSCs) have been reported to localize in colorectal carcinomas, and participate in the formation of the tumor microenvironment. They have recently been isolated from colorectal cancer tissues, and are implicated in the growth, invasion, and metastasis of cancer cells. However, the roles and deta...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-017-0176-3

    authors: Zhang X,Hu F,Li G,Li G,Yang X,Liu L,Zhang R,Zhang B,Feng Y

    更新日期:2018-01-18 00:00:00