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
Oncogenejournal_title
Oncogeneauthors
Zhao Y,Qiao S,Hou X,Tian H,Deng S,Ye K,Nie Y,Chen X,Yan H,Tian Wdoi
10.1038/s41388-019-0719-4subject
Has Abstractpub_date
2019-05-01 00:00:00pages
4297-4309issue
22eissn
0950-9232issn
1476-5594pii
10.1038/s41388-019-0719-4journal_volume
38pub_type
杂志文章相关文献
ONCOGENE文献大全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
更新日期:2001-08-30 00:00:00
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:
更新日期:1989-04-01 00:00:00
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
更新日期:2017-02-23 00:00:00
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:
更新日期:1996-10-17 00:00:00
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
更新日期:2017-08-31 00:00:00
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
更新日期:2006-06-01 00:00:00
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
更新日期:2014-06-12 00:00:00
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:
更新日期:1992-05-01 00:00:00
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
更新日期:2000-08-10 00:00:00
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:
更新日期:1995-02-16 00:00:00
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
更新日期:2007-04-19 00:00:00
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
更新日期:2007-04-05 00:00:00
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
更新日期:1997-02-06 00:00:00
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
更新日期:2007-04-26 00:00:00
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
更新日期:2006-01-19 00:00:00
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
更新日期:2013-01-24 00:00:00
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
更新日期:2015-04-16 00:00:00
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
更新日期:2013-05-16 00:00:00
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
更新日期:2012-08-02 00:00:00
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
更新日期:2001-11-15 00:00:00
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
更新日期:2001-08-02 00:00:00
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
更新日期:2017-08-24 00:00:00
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
更新日期:1998-04-23 00:00:00
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
更新日期:2011-02-10 00:00:00
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
更新日期:2012-07-05 00:00:00
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
更新日期:2002-01-10 00:00:00
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
更新日期:2007-01-04 00:00:00
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:
更新日期:1993-07-01 00:00:00
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
更新日期:2015-06-04 00:00:00
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
更新日期:2005-04-28 00:00:00