Abstract:
:TNFα is a pleiotropic cytokine which fuels tumor cell growth, invasion, and metastasis in some malignancies, while in others it induces cytotoxic cell death. However, the molecular mechanism by which TNFα exerts its diverse effects on breast cancer subtypes remains elusive. Using in vitro assays and mouse xenografts, we show here that TNFα contributes to the aggressive properties of triple negative breast cancer (TNBC) cell lines via upregulation of TNFAIP3(A20). In a striking contrast, TNFα induces a potent cytotoxic cell death in luminal (ER+) breast cancer cell lines which fail to upregulate A20 expression. Overexpression of A20 not only protects luminal breast cancer cell lines from TNFα-induced cell death via inducing HSP70-mediated anti-apoptotic pathway but also promotes a robust EMT/CSC phenotype by activating the pStat3-mediated inflammatory signaling. Furthermore, A20 overexpression in luminal breast cancer cells induces aggressive metastatic properties in mouse xenografts via generating a permissive inflammatory microenvironment constituted by granulocytic-MDSCs. Collectively, our results reveal a mechanism by which A20 mediates pleiotropic effects of TNFα playing role in aggressive behaviors of TNBC subtype while its deficiency results in TNFα-induced apoptotic cell death in luminal breast cancer subtype.
journal_name
Oncogenejournal_title
Oncogeneauthors
Lee E,Ouzounova M,Piranlioglu R,Ma MT,Guzel M,Marasco D,Chadli A,Gestwicki JE,Cowell JK,Wicha MS,Hassan KA,Korkaya Hdoi
10.1038/s41388-018-0472-0subject
Has Abstractpub_date
2019-01-01 00:00:00pages
469-482issue
4eissn
0950-9232issn
1476-5594pii
10.1038/s41388-018-0472-0journal_volume
38pub_type
杂志文章相关文献
ONCOGENE文献大全abstract::Cancer cells lose homeostatic flexibility because of mutations and dysregulated signaling pathways involved in maintaining homeostasis. Tuberous Sclerosis Complex 1 (TSC1) and TSC2 play a fundamental role in cell homeostasis, where signal transduction through TSC1/TSC2 is often compromised in cancer, leading to aberra...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-018-0381-2
更新日期:2018-11-01 00:00:00
abstract::Density-enhanced protein-tyrosine phosphatase-1 (DEP-1 also CD148) is a transmembrane molecule with a single intracellular PTP domain. It has recently been proposed to function as a tumor suppressor. We have previously shown that DEP-1 dephosphorylates the activated platelet-derived growth factor (PDGF) beta-receptor ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206652
更新日期:2003-07-03 00:00:00
abstract::SHPTP2 is a ubiquitously-expressed SH2-containing tyrosine phosphatase that is tyrosine phosphorylated in response to activation of various receptor and nonreceptor tyrosine kinases. SHPTP2 associates with the platelet-derived growth factor (PDGF) receptor after ligand stimulation, and binding of SHPTP2 to this recept...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1996-04-04 00:00:00
abstract::The Crk II adaptor protein encodes an SH2/SH3-domain containing adaptor protein with an SH2-SH3-SH3 domain structure that transmits signals from tyrosine kinases. The two SH3 domains are separated by a 54 amino acid linker region, whose length is highly conserved in xenopus, chicken, and mamalian Crk II proteins. To g...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204173
更新日期:2001-02-22 00:00:00
abstract::Promoter methylation is an important pathway in transcriptional silencing of known and candidate tumor suppressor genes in Head and Neck Squamous Cell Carcinoma (HNSCC). In order to study the association of tumor suppressor gene promoter methylation in HNSCC with patient clinical characteristics, especially alcohol co...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205528
更新日期:2002-06-20 00:00:00
abstract::The regulatory step in ubiquitin (Ub)-mediated protein degradation involves recognition and selection of the target substrate by an E3 Ub-ligase. E3 Ub-ligases evoke sophisticated mechanisms to regulate their activity temporally and spatially, including multiple post-translational modifications, combinatorial E3 Ub-li...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1208614
更新日期:2005-04-18 00:00:00
abstract::Oncolytic adenoviruses, such as Delta-24-RGD (Δ24RGD), are replication-competent viruses that are genetically engineered to induce selective cancer cell lysis. In cancer cells, Δ24RGD induces massive autophagy, which is required for efficient cell lysis and adenoviral spread. Understanding the cellular mechanisms unde...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2014.452
更新日期:2015-10-08 00:00:00
abstract::Recurrent and hormone-refractory prostate cancer (PCA) exhibits aggressive behaviors while current therapeutic approaches show little effect of prolonging the survival of patients with PCA. Thus, a deeper understanding of the patho-molecular mechanisms underlying the disease progression in PCA is crucial to identify n...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-018-0497-4
更新日期:2019-02-01 00:00:00
abstract::Radicicol, an inhibitor of Src-family protein-tyrosine kinases, causes morphological reversion of v-src- and v-Ha-ras-transformed fibroblasts and arrest of the cell cycle at both the G1 and the G2 phases. Radicicol was found to inhibit the growth of several other oncogene-transformed cell lines and human carcinoma cel...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201443
更新日期:1997-11-20 00:00:00
abstract::Ultraviolet (UV) light is a potent mutagenic and genotoxic agent. Whereas DNA damage induced by UV light is known to be responsible for UV-induced genotoxicity, its role in triggering apoptosis is still unclear. We addressed this issue by comparing nucleotide excision repair (NER) deficient 27-1 and 43-3B Chinese hams...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204754
更新日期:2001-09-20 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::Ovarian cancer (OvCa) is characterized by widespread and rapid metastasis in the peritoneal cavity. Visceral adipocytes promote this process by providing fatty acids (FAs) for tumour growth. However, the exact mechanism of FA transfer from adipocytes to cancer cells remains unknown. This study shows that OvCa cells co...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-017-0093-z
更新日期:2018-04-01 00:00:00
abstract::The microenvironment of glioblastoma (GBM) contains high levels of inflammatory cytokine interleukin 6 (IL-6), which contributes to promote tumour progression and invasion. The common epidermal growth factor receptor variant III (EGFRvIII) mutation in GBM is associated with significantly higher levels of IL-6. Further...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2014.225
更新日期:2015-05-28 00:00:00
abstract::Predisposition to melanoma is genetically heterogeneous. Two high penetrance susceptibility genes, CDKN2A and CDK4, have so far been identified and mapping is ongoing to localize and identify others. With the advent of a catalogue of millions of potential DNA polymorphisms, attention is now also being focused on ident...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1206445
更新日期:2003-05-19 00:00:00
abstract::The transcription factor E2F activates genes required for S phase, such as cyclin E and cyclin A. We show that, contrary to long term effects of E2F-1 overexpression, short ectopic overexpression of this transcription factor in logarithmically growing cells does neither affect the cell cycle distribution nor the cell ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201061
更新日期:1997-05-15 00:00:00
abstract::The membrane-anchored MMP-regulator RECK is down regulated in many solid tumors; the extent of RECK down regulation correlates with poor prognosis. Forced expression of RECK in tumor cells results in suppression of angiogenesis, invasion, and metastasis. Studies on the roles and the mechanisms of regulation of the REC...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208733
更新日期:2005-09-01 00:00:00
abstract::Inactivation of tumor-suppressor genes is one of the key hallmarks of a tumor. Unlike other tumor-suppressor genes, p53 is inactivated by missense mutations in half of all human cancers. It has become increasingly clear that the resulting mutant p53 proteins do not represent only the mere loss of wild-type p53 tumor s...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1210296
更新日期:2007-04-02 00:00:00
abstract::Recognition and elimination of malignant cells by cytotoxic T lymphocytes depends on antigenic peptides generated by proteasomes. It has been established that impairment of the immunoproteasome subunits, that is, PSMB8, PSMB9 and PSMB10 (PSMBs), is critical for malignant cells to escape immune recognition. We report h...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2013.224
更新日期:2014-05-22 00:00:00
abstract::A candidate gene (WT1) has recently been described for the 11p13 tumour-suppressor gene involved in the development of Wilms' tumour. This gene encodes a zinc finger protein which can bind to a specific DNA sequence. We have found a 226 base deletion in the mRNA from a unilateral Wilms' tumour, which would cause a fra...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1992-04-01 00:00:00
abstract::We have used two different, but complementary assays to characterize functions of SV40 T antigen that are necessary for its ability to immortalize rat embryo fibroblasts. In accordance with previous work, we found that several functions were required. These include activities that map to the p53 binding domain and the...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203154
更新日期:1999-12-02 00:00:00
abstract::The Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) has a significant role in initiating EBV-associated lymphoproliferative disease and EBV-related malignancies. In view of clinical features related to the type of EBV latency, LMP1 may influence invasiveness of EBV associated tumors categorized as ty...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203502
更新日期:2000-03-30 00:00:00
abstract::Neuroendocrine prostate cancer (NEPC) has increasingly become a clinical challenge. The mechanisms by which neuroendocrine (NE) cells arises from prostate adenocarcinoma cells are poorly understood. FOXA1 is a transcription factor of the forkhead family that is required for prostate epithelial differentiation. In this...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2017.50
更新日期:2017-07-13 00:00:00
abstract::The role of the hepatitis B virus protein HBx in liver cell proliferation and apoptosis remains controversial. Using a transgenic mouse model, we have recently shown that HBx stimulates the apoptotic turnover of hepatocytes, independently of p53. In this paper, we tested whether the proapoptotic function of HBx can in...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205110
更新日期:2002-01-17 00:00:00
abstract::Head and neck squamous carcinomas (HNSCC) present as dense epithelioid three-dimensional (3D) tumor nests that can mediate signals via the human epidermal growth factor receptor (ErbB) tyrosine kinase family to promote intratumoral survival and growth. We examined the role of the tumor microenvironment on ErbB recepto...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2015.220
更新日期:2016-03-24 00:00:00
abstract::Oligonucleotide microarray analysis was applied to assess the expression profile of 332 probe sets representing 308 genes or expressed sequence tags (ESTs) that map to chromosome 17 in order to address epigenetic events that result in alterations in gene expression in epithelial ovarian cancer (EOC). Expression profil...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206219
更新日期:2003-03-13 00:00:00
abstract::Cyclooxygenase (COX)-2 is upregulated in hepatocellular carcinoma (HCC). However, the direct causative effect of COX-2 in spontaneous HCC formation remains unknown. We thus investigate the role and molecular pathogenesis of COX-2 in HCC by using liver-specific COX-2 transgenic (TG) mice. We found spontaneous HCC forma...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2017.73
更新日期:2017-08-01 00:00:00
abstract::Hox genes encode DNA-binding proteins that are deployed in overlapping domains along various body axes during embryonic development. This sequential activation of Hox genes in temporal and spatial mode, the Hox code, is critical for the proper positioning of segmented structures along those axes, which include the ver...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/onc.2010.484
更新日期:2011-01-27 00:00:00
abstract::Epidemiological studies have demonstrated a close association of type 2 diabetes and hepatocellular carcinoma (HCC). Exenatide (Ex-4), a potent diabetes drug targeting glucagon-like peptide-1 receptor (GLP-1R), is protective against non-alcoholic fatty liver disease (NAFLD). However, the Ex-4 function and GLP-1R statu...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2017.38
更新日期:2017-07-20 00:00:00
abstract::Pin1 regulates a subset of phosphoproteins by isomerizing phospho-Ser/Thr-Pro motifs via a 'post-phosphorylation' mechanism. Here, we characterize TR3 as a novel Pin1 substrate, and the mitogenic function of TR3 depends on Pin1-induced isomerization. There are at least three phospho-Ser-Pro motifs on TR3 that bind to ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.463
更新日期:2012-06-07 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