Bioengineered tumor microenvironments with naked mole rats high-molecular-weight hyaluronan induces apoptosis in breast cancer cells.

Abstract:

:The naked mole rat (nmr) is cancer resistant due to the abundant production of extremely high-molecular-weight hyaluronan (EHMW-HA). However, whether EHMW-HA has similar anti-cancer effects in mice and humans remains to be determined. The present study used breast cancer cells to clarify the effect of EHMW-HA on breast cancer. First, the overexpression of nmrHas2 in 4T1 and BT549 cell lines in both two-dimensional (2D) and three-dimensional (3D) models to mimic tumor microenvironment was established. The 4T1/BT549-nmrHas2 cells could secrete EHMW-HA (with a molecular weight of up to 6 MDa), which was similar to that found in the naked mole rat. Second, EHMW-HA altering tumor microenvironment in both 2D monolayers and 3D spheroids significantly enhanced apoptosis, inhibiting the proliferation of 4T1 and BT549 cells. The prominent anticancer effects of EHMW-HA on the cancer-cell apoptosis phenotype were further confirmed by inhibiting tumor formation in nude mice. Finally, EHMW-HA significantly induced higher p53 protein expression, which enhanced pro-apoptotic proteins p21 and Bax in breast cancer cells; this is in contrast with the triggering of hypersensitivity of the naked mole rat cells to early contact inhibition (ECI). These results have important implications for the design of therapeutic approaches based on the application of EHMW-HA.

journal_name

Oncogene

journal_title

Oncogene

authors

Zhao Y,Qiao S,Hou X,Tian H,Deng S,Ye K,Nie Y,Chen X,Yan H,Tian W

doi

10.1038/s41388-019-0719-4

subject

Has Abstract

pub_date

2019-05-01 00:00:00

pages

4297-4309

issue

22

eissn

0950-9232

issn

1476-5594

pii

10.1038/s41388-019-0719-4

journal_volume

38

pub_type

杂志文章

相关文献

ONCOGENE文献大全
  • HACS1 encodes a novel SH3-SAM adaptor protein differentially expressed in normal and malignant hematopoietic cells.

    abstract::SH3 and SAM domains are protein interaction motifs that are predominantly seen in signaling molecules, adaptors, and scaffold proteins. We have identified a novel family of putative adaptor genes that includes HACS1. HACS1 encodes a 441 amino acid protein that is differentially expressed in hematopoietic cells and has...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1204698

    authors: Claudio JO,Zhu YX,Benn SJ,Shukla AH,McGlade CJ,Falcioni N,Stewart AK

    更新日期:2001-08-30 00:00:00

  • Activation of oncogenes in human oral cancer cells: a novel codon 13 mutation of c-H-ras-1 and concurrent amplifications of c-erbB-1 and c-myc.

    abstract::By NIH3T3 transfection assay in conjunction with in vitro transient neomycin selection, activated c-H-ras-1 oncogenes were detected in two squamous cell carcinoma cell lines, ZA and HOC-313, newly established from human oral cancer patients. ZA had a point mutational activation at the 13th codon, this activation of c-...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Tadokoro K,Ueda M,Ohshima T,Fujita K,Rikimaru K,Takahashi N,Enomoto S,Tsuchida N

    更新日期:1989-04-01 00:00:00

  • Twist1 promotes breast cancer invasion and metastasis by silencing Foxa1 expression.

    abstract::The heterogeneous breast cancers can be classified into different subtypes according to their histopathological characteristics and molecular signatures. Foxa1 expression is linked with luminal breast cancer (LBC) with good prognosis, whereas Twist1 expression is associated with basal-like breast cancer (BLBC) with po...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2016.286

    authors: Xu Y,Qin L,Sun T,Wu H,He T,Yang Z,Mo Q,Liao L,Xu J

    更新日期:2017-02-23 00:00:00

  • A pancreatic cancer-specific expression profile.

    abstract::We present an approach making use of technology established in the context of the genome project to describe a pancreatic cancer-specific expression profile and to identify new potential disease genes or disease-associated-genes. By use of gridded arrays of pancreatic cancer cDNA libraries and differential hybridizati...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Gress TM,Müller-Pillasch F,Geng M,Zimmerhackl F,Zehetner G,Friess H,Büchler M,Adler G,Lehrach H

    更新日期:1996-10-17 00:00:00

  • MAGEA1 interacts with FBXW7 and regulates ubiquitin ligase-mediated turnover of NICD1 in breast and ovarian cancer cells.

    abstract::Melanoma-associated antigen A1 (MAGEA1) is member of the MAGE gene family that is expressed in male germ line cells and placenta under normal physiological conditions. Although MAGEA1's expression levels have been evaluated as one of the cancer testis (CT) antigens for immunotherapy in melanoma and several other cance...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2017.131

    authors: Zhao J,Wang Y,Mu C,Xu Y,Sang J

    更新日期:2017-08-31 00:00:00

  • Upregulation and activation of PKC alpha by ErbB2 through Src promotes breast cancer cell invasion that can be blocked by combined treatment with PKC alpha and Src inhibitors.

    abstract::Although ErbB2 is known to enhance breast cancer metastasis, the signaling events responsible for this remain elusive. Alpha-isozyme of protein kinase C (PKCalpha), which is involved in cancer development and progression, has been suggested to be activated by ErbB2 without direct evidence. In addition, the roles of PK...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1209361

    authors: Tan M,Li P,Sun M,Yin G,Yu D

    更新日期:2006-06-01 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...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2013.284

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

    更新日期:2014-06-12 00:00:00

  • Molecular cloning and characterization of the t(2;14) translocation associated with childhood chronic lymphocytic leukemia.

    abstract::Two rare cases of chronic lymphocytic leukemia (CLL) in children, patients AS and LH, have been found to be associated with a unique chromosomal translocation, t(2;14)(p13;q32). Previous studies have shown the breakpoints of this translocation to be in the gamma 2 switch region of the Ig heavy-chain locus on chromosom...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Richardson AL,Humphries CG,Tucker PW

    更新日期:1992-05-01 00:00:00

  • G2A is an oncogenic G protein-coupled receptor.

    abstract::G2A is a heptahelical cell surface protein that has recently been described as a potential tumor suppressor, based on its ability to counteract transformation of pre-B cells and fibroblasts by Bcr-Abl, an oncogenic tyrosine kinase. We have isolated cDNAs encoding G2A in the course of screening libraries for clones tha...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1203731

    authors: Zohn IE,Klinger M,Karp X,Kirk H,Symons M,Chrzanowska-Wodnicka M,Der CJ,Kay RJ

    更新日期:2000-08-10 00:00:00

  • Wild-type p53 modulates apoptosis of normal, IL-3 deprived, hematopoietic cells.

    abstract::Apoptotic cell death is an active process which regulates the maintenance of the hematopoietic homeostasis. It has been reported that wild-type p53 (wt-p53) protein induces apoptosis in leukemia cells. To assess whether p53 is involved in the apoptotic process of normal hematopoietic cells, we introduced the temperatu...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Blandino G,Scardigli R,Rizzo MG,Crescenzi M,Soddu S,Sacchi A

    更新日期:1995-02-16 00:00:00

  • Human cancer cells require ATR for cell cycle progression following exposure to ionizing radiation.

    abstract::The vast majority of cancer cells have defective checkpoints that permit the cell cycle to progress in the presence of double-strand DNA breaks (DSBs) caused by ionizing radiation (IR) and radiomimetic drugs. ATR (ataxia telangiectasia-mutated and Rad3-related) has recently been shown to be activated by DSBs, although...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1210049

    authors: Hurley PJ,Wilsker D,Bunz F

    更新日期:2007-04-19 00:00:00

  • A novel Bcl-2/Bcl-X(L)/Bcl-w inhibitor ABT-737 as therapy in multiple myeloma.

    abstract::Bcl-2 or Bcl-X(L) confers resistance to chemotherapy in multiple myeloma (MM). Here we characterized the effects of ABT-737, a potent small-molecule inhibitor of antiapoptotic proteins Bcl-2, Bcl-X(L) and Bcl-w with markedly higher affinity than previously reported compounds, on human MM cells. ABT-737 induces apoptos...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1210028

    authors: Chauhan D,Velankar M,Brahmandam M,Hideshima T,Podar K,Richardson P,Schlossman R,Ghobrial I,Raje N,Munshi N,Anderson KC

    更新日期:2007-04-05 00:00:00

  • Absence of p53 permits propagation of mutant cells following genotoxic damage.

    abstract::Much evidence has been gathered in support of a critical role for p53 in the cellular response to DNA damage. p53 dysfunction is associated with progression and poor prognosis of many human cancers and with a high incidence of tumours in p53 knockout mice. The absence of a p53-dependent G1 arrest that facilitates DNA ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1200871

    authors: Griffiths SD,Clarke AR,Healy LE,Ross G,Ford AM,Hooper ML,Wyllie AH,Greaves M

    更新日期:1997-02-06 00:00:00

  • Targeting an E2F site in the mouse genome prevents promoter silencing in quiescent and post-mitotic cells.

    abstract::Previous studies have shown that the cell cycle-regulated B-myb promoter contains a conserved E2F binding site that is critical for repressing transcription in quiescent cells. To investigate its significance for permanent promoter silencing, we have inactivated this binding site in the mouse genome. Mice homozygous f...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1210087

    authors: Tavner F,Frampton J,Watson RJ

    更新日期:2007-04-26 00:00:00

  • Human T-cell leukemia virus type 1 Tax attenuates gamma-irradiation-induced apoptosis through physical interaction with Chk2.

    abstract::Checkpoint kinase 2 (Chk2) is known to mediate diverse cellular responses to genotoxic stress. The fundamental role of Chk2 is to regulate the network of genome-surveillance pathways that coordinate cell-cycle progression with DNA repair and cell survival or death. Defects in Chk2 contribute to the development of both...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1209059

    authors: Park HU,Jeong SJ,Jeong JH,Chung JH,Brady JN

    更新日期:2006-01-19 00:00:00

  • MTBP suppresses cell migration and filopodia formation by inhibiting ACTN4.

    abstract::Murine double minute (MDM2) binding protein (MTBP) has been implicated in cancer progression. Here, we demonstrate one mechanism by which MTBP inhibits cancer metastasis. Overexpression of MTBP in human osteosarcoma cell lines lacking wild-type p53 did not alter primary tumor growth in mice, but significantly inhibite...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2012.69

    authors: Agarwal N,Adhikari AS,Iyer SV,Hekmatdoost K,Welch DR,Iwakuma T

    更新日期:2013-01-24 00:00:00

  • Stem cell programs are retained in human leukemic lymphoblasts.

    abstract::Leukemic lymphoblasts within different immunophenotypic populations possess stem cell properties. However, whether or not the self-renewal program is retained from stem cells or conferred on progenitors by leukemogenic molecules remains unknown. We have addressed the issue in the context of TEL-AML1-associated acute l...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2014.148

    authors: Fan D,Zhou X,Li Z,Li ZQ,Duan C,Liu T,Zhang F,Huang Y,Zhang Y,Gao F,Guo Y,Gupta R,Chen G,Enver T,Tang J,Hong D

    更新日期:2015-04-16 00:00:00

  • Cell-penetrating H4 tail peptides potentiate p53-mediated transactivation via inhibition of G9a and HDAC1.

    abstract::Histone acetylation has a central role in establishing an active chromatin environment. The functional contribution of histone acetylation to chromatin transcription is accomplished by a dominant action of histone acetyltransferases over repressive histone-modifying activities at gene promoters; misregulation of these...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2012.273

    authors: Heo K,Kim JS,Kim K,Kim H,Choi J,Yang K,An W

    更新日期:2013-05-16 00:00:00

  • Repression of cancer cell senescence by PKCι.

    abstract::Senescence is an irreversible growth arrest phenotype adopted by cells that has a key role in protecting organisms from cancer. There is now considerable interest in therapeutic strategies that reactivate this process to control the growth of cancer cells. Protein kinase-Cι (PKCι) is a member of the atypical PKC famil...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2011.524

    authors: Paget JA,Restall IJ,Daneshmand M,Mersereau JA,Simard MA,Parolin DA,Lavictoire SJ,Amin MS,Islam S,Lorimer IA

    更新日期:2012-08-02 00:00:00

  • Cell density mediated pericellular hypoxia leads to induction of HIF-1alpha via nitric oxide and Ras/MAP kinase mediated signaling pathways.

    abstract::Environmental signals in the cellular milieu such as hypoxia, growth factors, extracellular matrix (ECM), or cell-surface molecules on adjacent cells can activate signaling pathways that communicate the state of the environment to the nucleus. Several groups have evaluated gene expression or signaling pathways in resp...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1204972

    authors: Sheta EA,Trout H,Gildea JJ,Harding MA,Theodorescu D

    更新日期:2001-11-15 00:00:00

  • Mel-CAM-specific genetic suppressor elements inhibit melanoma growth and invasion through loss of gap junctional communication.

    abstract::Normal human melanocytes are interspersed singly among keratinocytes along the basement membrane of the epidermis, whereas melanoma cells readily adhere to each other during invasion of the dermis or distant organs. The tumorigenic and metastatic phenotype of melanoma cells often correlates with increased expression o...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1204616

    authors: Satyamoorthy K,Muyrers J,Meier F,Patel D,Herlyn M

    更新日期:2001-08-02 00:00:00

  • MRE11 stability is regulated by CK2-dependent interaction with R2TP complex.

    abstract::The MRN (MRE11-RAD50-NBS1) complex is essential for repair of DNA double-strand breaks and stalled replication forks. Mutations of the MRN complex subunit MRE11 cause the hereditary cancer-susceptibility disease ataxia-telangiectasia-like disorder (ATLD). Here we show that MRE11 directly interacts with PIH1D1, a subun...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2017.99

    authors: von Morgen P,Burdova K,Flower TG,O'Reilly NJ,Boulton SJ,Smerdon SJ,Macurek L,Hořejší Z

    更新日期:2017-08-24 00:00:00

  • Epidermal growth factor activation of NF-kappaB is mediated through IkappaBalpha degradation and intracellular free calcium.

    abstract::The transcription factor NF-kappa-B is normally sequestered in the cytoplasm by its inhibitory subunit IkappaB. Most extracellular signals activate NF-kappa-B through a mechanism involving the phosphorylation and proteasome-dependent degradation of IkappaB. EGF activates NF-kappaB in A-431 carcinoma cells, which overe...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1201731

    authors: Sun L,Carpenter G

    更新日期:1998-04-23 00:00:00

  • Identifying LRRC16B as an oncofetal gene with transforming enhancing capability using a combined bioinformatics and experimental approach.

    abstract::Oncofetal genes are expressed in embryos or fetuses, are downregulated or undetectable in adult tissues, and then re-expressed in tumors. Known oncofetal genes, such as AFP, GCB, FGF18, IMP-1 and SOX1, often have important clinical applications or pivotal biological functions. To find new oncofetal-like genes, we used...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2010.451

    authors: Hsu CC,Chiang CW,Cheng HC,Chang WT,Chou CY,Tsai HW,Lee CT,Wu ZH,Lee TY,Chao A,Chow NH,Ho CL

    更新日期:2011-02-10 00:00:00

  • The nuclear receptor TR3 regulates mTORC1 signaling in lung cancer cells expressing wild-type p53.

    abstract::The orphan nuclear receptor TR3 (NR41A and Nur77) is overexpressed in most lung cancer patients and is a negative prognostic factor for patient survival. The function of TR3 was investigated in non-small-cell lung cancer A549 and H460 cells, and knockdown of TR3 by RNA interference (siTR3) inhibited cancer cell growth...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2011.504

    authors: Lee SO,Andey T,Jin UH,Kim K,Singh M,Safe S

    更新日期:2012-07-05 00:00:00

  • Low plasma levels of matrix metalloproteinase 9 permit increased tumor angiogenesis.

    abstract::Angiogenesis is essential for tumor growth and blocking this process might be a valid tool for the control of cancer growth. We showed previously that tumor angiogenesis in integrin alpha1-null mice is reduced compared to that of wild type animals and that over-expression of matrix metalloproteinase 9 (MMP-9) in the a...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1205045

    authors: Pozzi A,LeVine WF,Gardner HA

    更新日期:2002-01-10 00:00:00

  • Direct cancer tissue proteomics: a method to identify candidate cancer biomarkers from formalin-fixed paraffin-embedded archival tissues.

    abstract::Successful treatment of multiple cancer types requires early detection and identification of reliable biomarkers present in specific cancer tissues. To test the feasibility of identifying proteins from archival cancer tissues, we have developed a methodology, termed direct tissue proteomics (DTP), which can be used to...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1209755

    authors: Hwang SI,Thumar J,Lundgren DH,Rezaul K,Mayya V,Wu L,Eng J,Wright ME,Han DK

    更新日期:2007-01-04 00:00:00

  • Two wnt genes in Caenorhabditis elegans.

    abstract::wnt genes encode secretory glycoproteins that have been implicated in growth control and development in mice, frogs and insects. In this report we examine properties of two wnt genes recently identified in the nematode Caenorhabditis elegans. The first gene, Ce-wnt-1, was previously identified by a polymerase chain re...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Shackleford GM,Shivakumar S,Shiue L,Mason J,Kenyon C,Varmus HE

    更新日期:1993-07-01 00:00:00

  • Tumor heterogeneity and plasticity as elusive drivers for resistance to MAPK pathway inhibition in melanoma.

    abstract::Despite the recent success of MAPK signaling-targeted drugs in melanoma, the majority of patients with metastatic melanoma still undergo disease progression after initial tumor shrinkage indicating gradually developing therapy resistance. This review will give an overview on currently suggested concepts of resistance ...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/onc.2014.249

    authors: Roesch A

    更新日期:2015-06-04 00:00:00

  • The oncogene PDGF-B provides a key switch from cell death to survival induced by TNF.

    abstract::Tumor necrosis factor (TNF) induces both cell death and survival signals. NF-kappaB, a transcription factor activated by TNF, is critical for controlling survival signals through trans-activation of downstream target genes. However, few NF-kappaB target survival genes have been identified with direct roles in oncogene...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1208516

    authors: Au PY,Martin N,Chau H,Moemeni B,Chia M,Liu FF,Minden M,Yeh WC

    更新日期:2005-04-28 00:00:00