The helicase HAGE prevents interferon-α-induced PML expression in ABCB5+ malignant melanoma-initiating cells by promoting the expression of SOCS1

Mathieu, Morgan G.; Miles, Amanda K.; Ahmad, Murrium; Buczek, Magdalena Elżbieta; Pockley, A. Graham; Rees, Robert C.; Regad, Tarik

doi:10.1038/cddis.2014.29

Cited by 16 publications

(16 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The experimental procedures were performed as described previously. 30 For IB, the cells lysed in 1 × solution containing 50 m M Tris-HCl (pH 6.8), 100 m M dithiothreitol, 2% (w/v) SDS, 0.1% (w/v) bromophenol blue and 10% (v/v) glycerol, and loaded onto Tris/glycine SDS–polyacrylamide gels for electrophoresis. The proteins were transferred onto Amersham Hybond-P PVDF membranes (GE Healthcare, Chalfont St Giles, Buckinghamshire, UK).…”

Section: Methodsmentioning

confidence: 99%

Cytoplasmic PML promotes TGF-β-associated epithelial–mesenchymal transition and invasion in prostate cancer

et al. 2015

Self Cite

View full text Add to dashboard Cite

Epithelial–mesenchymal transition (EMT) is a key event that is involved in the invasion and dissemination of cancer cells. Although typically considered as having tumour-suppressive properties, transforming growth factor (TGF)-β signalling is altered during cancer and has been associated with the invasion of cancer cells and metastasis. In this study, we report a previously unknown role for the cytoplasmic promyelocytic leukaemia (cPML) tumour suppressor in TGF-β signalling-induced regulation of prostate cancer-associated EMT and invasion. We demonstrate that cPML promotes a mesenchymal phenotype and increases the invasiveness of prostate cancer cells. This event is associated with activation of TGF-β canonical signalling pathway through the induction of Sma and Mad related family 2 and 3 (SMAD2 and SMAD3) phosphorylation. Furthermore, the cytoplasmic localization of promyelocytic leukaemia (PML) is mediated by its nuclear export in a chromosomal maintenance 1 (CRM1)-dependent manner. This was clinically tested in prostate cancer tissue and shown that cytoplasmic PML and CRM1 co-expression correlates with reduced disease-specific survival. In summary, we provide evidence of dysfunctional TGF-β signalling occurring at an early stage in prostate cancer. We show that this disease pathway is mediated by cPML and CRM1 and results in a more aggressive cancer cell phenotype. We propose that the targeting of this pathway could be therapeutically exploited for clinical benefit.

show abstract

Section: Methodsmentioning

confidence: 99%

Cytoplasmic PML promotes TGF-β-associated epithelial–mesenchymal transition and invasion in prostate cancer

et al. 2015

Self Cite

View full text Add to dashboard Cite

show abstract

“…In the current study, with Mel526 cells as the experimental model, it was found that silencing SOCS1 can improve IFN-γ sensitivity, thus providing a novel approach to improve the efficacy of melanoma immunotherapy. However, for different types of melanoma as the experimental models, the experimental results can differ (30). Thus, a number of factors should be integrated in the clinical translational research, including pathological features and hormone-dependency.…”

Section: Discussionmentioning

confidence: 99%

Effects of suppressor of cytokine signaling 1 silencing on human melanoma cell proliferation and interferon-γ sensitivity

Xu¹,

Wang

Gou³

et al. 2014

Molecular Medicine Reports

View full text Add to dashboard Cite

The aim of the current study was to observe the effects of suppressor of cytokine signaling 1 (SOCS1) silencing in human melanoma cells on cell biological behavior and interferon-γ (IFN-γ) sensitivity, and to investigate the use of SOCS1 as a therapeutic target in the treatment of melanoma. Western blot analysis and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to verify that SOCS1 interference effectively silenced the expression of SOCS1 in the Mel526 human melanoma cell line. For IFN-γ stimulation, western blot analysis was used to observe changes in expression levels of signal transduction and transcription activator (STAT) 1 and phosphorylated STAT (pSTAT) 1. Changes in the expression levels of IFN-γ regulatory factor 1 (IRF-1) were measured with RT-qPCR. Changes in the sensitivity of melanoma cells to IFN-γ were detected using an MTT assay. The cell proliferation rate was observed by cell counting and changes in the cell cycle were detected with flow cytometry. The results revealed that SOCS1 interference effectively silences SOCS1 expression in Mel526 cells. However, the S stage of the cell cycle was markedly extended. Following the inhibition of SOCS1 expression, the proliferation experiment demonstrated that the proliferation ability of Mel526 cells was decreased. Following IFN-γ stimulation, the expression levels of pSTAT and IRF-1 increased significantly compared with those in the controls. The MTT experiment showed that SOCS1 interference caused the median inhibitory concentration (IC50) of oxaliplatin in Mel526 cells to decrease significantly. In conclusion, SOCS1 interference reduced the proliferation ability of Mel526 human melanoma cells and increased their sensitivity to IFN-γ.

show abstract

“…These resistance mechanisms include the destruction of cancer apoptotic pathways, excessive activation of aberrant signaling pathways leading to tumor growth and survival, induction of the expression of ABC drug efflux transporters [84,85]. ABCB5, is a human multi-drug resistance (MDR) P-glycoprotein family member, which mediates chemo-resistance in melanoma via its function as a drug efflux transporter [86,87]. The expression of ABCB5 is associated with increased level of tumor antigen P97, a melanotransferrin (MTf) that is associated with melanoma growth [88].…”

Section: Mechanisms Of Melanoma Stem-like Cells-mediated Chemo-resistmentioning

confidence: 99%

Cancer Stem- Like Cells in Melanoma Progression, Resistance and Recurrence: Significance for Melanoma Treatment

Hassan¹,

A²,

Haïkel³

et al. 2014

IJST

View full text Add to dashboard Cite

Human malignant melanoma is a highly aggressive tumor which demonstrates heterogeneity and a propensity to drug resistance. Despite improved treatment options, patients with advanced malignant melanoma continue have a poor prognosis as measured by progression-free and overall survival. The cancer stem-like cell (CSC) hypothesis suggests that neoplastic clones are maintained by a small fraction of cells with stem cell properties. As has been demonstrated with other tumor types, melanoma progression, resistance to chemo-and radiotherapy, and recurrence can be attributed to a small fraction of cells termed melanoma stem-like cells (MSCs). These MSCs are characterized by a distinct protein patterns and aberrant signaling pathways, which are either in a causal or consequential relationship to tumor progression, drug resistance and recurrence. This review focuses on the mechanistic role of MSCs leading to tumor progression and metastasis, resistance and recurrence. Understanding the molecular mechanisms underlying MSCs migration, invasion, resistance to standard treatments, and recurrence may help to improve current therapeutic modalities and/or pave the way for the development of new therapeutical management strategy for tumor treatment.

show abstract

The helicase HAGE prevents interferon-α-induced PML expression in ABCB5+ malignant melanoma-initiating cells by promoting the expression of SOCS1

Cited by 16 publications

References 33 publications

Cytoplasmic PML promotes TGF-β-associated epithelial–mesenchymal transition and invasion in prostate cancer

Cytoplasmic PML promotes TGF-β-associated epithelial–mesenchymal transition and invasion in prostate cancer

Effects of suppressor of cytokine signaling 1 silencing on human melanoma cell proliferation and interferon-γ sensitivity

Cancer Stem- Like Cells in Melanoma Progression, Resistance and Recurrence: Significance for Melanoma Treatment

Contact Info

Product

Resources

About