TRAF4 is potently induced by TAp63 isoforms and localised according to differentiation in SCCHN

Gu, Xiaolian; Coates, Philip J.; MacCallum, Stephanie F.; Boldrup, Linda; Sjöström, Björn; Nylander, Karin

doi:10.4161/cbt.6.12.5002

Cited by 17 publications

(13 citation statements)

References 26 publications

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“…As reported, TRAF4 was found to be overexpressed in various cancer cells (28), implying that TRAF4 overexpression is common in the majority of cancer cells, whereas TRAF4 also has an antitumor effect (36,37). Therefore, TRAF4 has different functions in different cancer cells, dependent on the microenvironment and stimulation.…”

Section: Discussionmentioning

confidence: 78%

MicroRNA-370 inhibits the progression of non-small cell lung cancer by downregulating oncogene TRAF4

et al. 2015

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Lung cancer is the leading cause of cancer-related deaths, of which most can be attributed to non-small cell lung cancer (NSCLC). microRNAs (miRNAs) are a group of small non-coding RNAs that focus on post-transcriptional modification. The present study aimed to investigate the role and function of microRNA-370 (miR-370) in NSCLC and explore the underlying functional mechanisms. We found that miR-370 was significantly downregulated in the tumor tissues of NSCLC patients as well as in NSCLC cell lines. Overexpression of miR-370 by infection of recombinant lentivirus markedly inhibited cell proliferation and promoted cell apoptosis of NSCLC cells. In addition, in vivo tumor formation of NSCLC cells was decreased by miR-370 overexpression. Through bioinformatic analysis, we found that tumor necrosis factor receptor-associated factor 4 (TRAF4), an oncogene as previously reported, was predicted as a putative target gene of miR-370. The direct targeting relationship between miR-370 and the 3'-untranslated region was validated by dual-luciferase reporter assay. Furthermore, overexpression of miR-370 downregulated the protein expression of TRAF4 in the NSCLC cells. Moreover, the growth inhibitory effect of miR-370 overexpression on NSCLC cells was abrogated by TRAF4 overexpression. In conclusion, our results suggest that miR-370 plays an important role in NSCLC by regulating TRAF4 and may be a potential target for the treatment of NSCLC.

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Section: Discussionmentioning

confidence: 78%

MicroRNA-370 inhibits the progression of non-small cell lung cancer by downregulating oncogene TRAF4

et al. 2015

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“…Binding of p63 to IGFBP3 in Box A and Box B has been shown previously 20; thus, IGFBP3 Box A has been used as a positive control in our laboratory. Recently we found binding of p63 to human TRAF4 promoter 21; TRAF4 was used as the positive control in this assay. Binding of p63 TRAF4 promoters was seen in the same samples used to analyse CD44 binding (Figure 2B).…”

Section: Resultsmentioning

confidence: 99%

ΔNp63 isoforms regulate CD44 and keratins 4, 6, 14 and 19 in squamous cell carcinoma of head and neck

Boldrup

Coates

et al. 2007

The Journal of Pathology

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The human p63 gene codes for multiple protein isoforms and is commonly over-expressed in squamous cell carcinoma of head and neck (SCCHN). This expression is predominantly of the DeltaN- and beta-isoforms, the former lacking the p53-related transactivation domain. p63 can activate or repress transcription of p53 and p73 target genes, but also has unique transcriptional targets and, unlike other p53 family members, is required for normal development and differentiation of squamous epithelia. We have identified novel targets of p63, using microarray analysis of SCCHN cells that stably over-express individual DeltaNp63 isoforms. All three isoforms induced expression of the cancer stem cell marker, CD44, with the DeltaNp63beta isoform showing strongest induction. Using chromatin immunoprecipitation, we were unable to show direct binding of p63 to the CD44 promoter, but found that p63 specifically increased expression of CD44 lacking variant exon 2. Each of the DeltaNp63 isoforms up-regulated expression of keratins 6A and 14 and down-regulated expression of keratins 4 and 19, in keeping with their expression patterns in SCCHN. The data strengthen the idea that p63 has key roles in regulating normal and abnormal differentiation processes through both induction and repression of genes with opposite functions. The identification of up-regulation and differential splicing of CD44 following p63 over-expression indicates roles in the regulation of adhesion, metastasis and the cancer stem cell phenotype.

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“…TRAF4 locates in the nucleus in normal oral epithelium and highly/moderately differentiated cells, but is localized in the cytoplasm in poorly differentiated SCCHN. Overexpression of TRAF4 in SCCHN induces apoptosis and suppresses colony formation [320][321][322]. Thus, TRAF4 overexpression has different outcomes in different carcinomas.…”

Section: Carcinomasmentioning

confidence: 99%

TRAF molecules in cell signaling and in human diseases

Xie

2013

JMS

391

454

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The tumor necrosis factor receptor (TNF-R)-associated factor (TRAF) family of intracellular proteins were originally identified as signaling adaptors that bind directly to the cytoplasmic regions of receptors of the TNF-R superfamily. The past decade has witnessed rapid expansion of receptor families identified to employ TRAFs for signaling. These include Toll-like receptors (TLRs), NOD-like receptors (NLRs), RIG-I-like receptors (RLRs), T cell receptor, IL-1 receptor family, IL-17 receptors, IFN receptors and TGFβ receptors. In addition to their role as adaptor proteins, most TRAFs also act as E3 ubiquitin ligases to activate downstream signaling events. TRAF-dependent signaling pathways typically lead to the activation of nuclear factor-κBs (NF-κBs), mitogen-activated protein kinases (MAPKs), or interferon-regulatory factors (IRFs). Compelling evidence obtained from germ-line and cell-specific TRAF-deficient mice demonstrates that each TRAF plays indispensable and non-redundant physiological roles, regulating innate and adaptive immunity, embryonic development, tissue homeostasis, stress response, and bone metabolism. Notably, mounting evidence implicates TRAFs in the pathogenesis of human diseases such as cancers and autoimmune diseases, which has sparked new appreciation and interest in TRAF research. This review presents an overview of the current knowledge of TRAFs, with an emphasis on recent findings concerning TRAF molecules in signaling and in human diseases.

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TRAF4 is potently induced by TAp63 isoforms and localised according to differentiation in SCCHN

Cited by 17 publications

References 26 publications

MicroRNA-370 inhibits the progression of non-small cell lung cancer by downregulating oncogene TRAF4

MicroRNA-370 inhibits the progression of non-small cell lung cancer by downregulating oncogene TRAF4

ΔNp63 isoforms regulate CD44 and keratins 4, 6, 14 and 19 in squamous cell carcinoma of head and neck

TRAF molecules in cell signaling and in human diseases

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