Cancers, Vol. 11, Pages 1806: Complex Formation with Monomeric α-Tubulin and Importin 13 Fosters c-Jun Protein Stability and Is Required for c-Jun’s Nuclear Translocation and Activity

Cancers, Vol. 11, Pages 1806: Complex Formation with Monomeric α-Tubulin and Importin 13 Fosters c-Jun Protein Stability and Is Required for c-Jun’s Nuclear Translocation and Activity Cancers doi: 10.3390/cancers11111806 Authors: Melanie Kappelmann-Fenzl Silke Kuphal Rosemarie Krupar Dirk Schadendorf Viktor Umansky Lily Vardimon Claus Hellerbrand Anja-Katrin Bosserhoff Microtubules are highly dynamic structures, which consist of α- and β-tubulin heterodimers. They are essential for a number of cellular processes, including intracellular trafficking and mitosis. Tubulin-binding chemotherapeutics are used to treat different types of tumors, including malignant melanoma. The transcription factor c-Jun is a central driver of melanoma development and progression. Here, we identify the microtubule network as a main regulator of c-Jun activity. Monomeric α-tubulin fosters c-Jun protein stability by protein–protein interaction. In addition, this complex formation is necessary for c-Jun’s nuclear localization sequence binding to importin 13, and consequent nuclear import and activity of c-Jun. A reduction in monomeric α-tubulin levels by treatment with the chemotherapeutic paclitaxel resulted in a decline in the nuclear accumulation of c-Jun in melanoma cells in an experimental murine model and in patients’ tissues. These findings add important knowledge to the mechanism of the actio...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research

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Angiopoietin-like protein 2 (ANGPTL2) is a secreted glycoprotein homologous to angiopoietins. Previous studies suggest that tumor cell-derived ANGPTL2 has tumor-promoting function. Here, we conducted mechanistic analysis comparing ANGPTL2 function in cancer progression in a murine syngeneic model of melanoma and a mouse model of translocation renal cell carcinoma (tRCC). ANGPTL2 deficiency in tumor cells slowed tRCC progression, supporting a tumor-promoting role. However, systemic ablation of ANGPTL2 accelerated tRCC progression, supporting a tumor-suppressing role. The syngeneic model also demonstrated a tumor-suppressing...
Source: Genes and Development - Category: Genetics & Stem Cells Authors: Tags: Research Papers Source Type: research
n-Anezin Oncogene-induced STAT3-activation is central to tumor progression by promoting cancer cell expression of pro-angiogenic and immunosuppressive factors. STAT3 is also activated in infiltrating immune cells including tumor-associated macrophages (TAM) amplifying immune suppression. Consequently, STAT3 is considered as a target for cancer therapy. However, its interplay with other STAT-family members or transcription factors such as NF-κB has to be considered in light of their concerted regulation of immune-related genes. Here, we discuss new attempts at re-educating immune suppressive tumor-associated m...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Abstract Earlier studies from our laboratory have demonstrated that Oxyresveratrol (OXY), a hydroxyl-substituted stilbene, exhibits potent inhibition of human melanoma cell proliferation. The present study defines a cytotoxic effect of OXY on the highly chemo-resistant, triple-negative human breast cancer cell line MDA-MB-231. OXY-mediated cell death resulted in accumulation of cells at the sub-G1 phase of the cell cycle, induced chromatin condensation, DNA fragmentation, phosphatidylserine externalization and PARP cleavage, indicative of apoptosis. Interestingly, morphology and cell viability studies with the pan...
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Biochem Pharmacol Source Type: research
ie Bogaerts Melittin (MEL), a small peptide component of bee venom, has been reported to exhibit anti-cancer effects in vitro and in vivo. However, its clinical applicability is disputed because of its non-specific cytotoxicity and haemolytic activity in high treatment doses. Plasma-treated phosphate buffered saline solution (PT-PBS), a solution rich in reactive oxygen and nitrogen species (RONS) can disrupt the cell membrane integrity and induce cancer cell death through oxidative stress-mediated pathways. Thus, PT-PBS could be used in combination with MEL to facilitate its access into cancer cells and to reduce the r...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
CONCLUSIONS: The priming of tumors with ADI-PEG20 and docetaxel results in the stabilization of c-MYC potentiating the effect of GEM treatment via an increase in hENT1 expression. This finding is applicable to ASS1-deficient cancers that are currently treated with GEM. PMID: 31113844 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
In this study, we found for the first time that an extracellular cytokine, S100A8/A9, accelerates breast cancer growth and metastasis upon binding to a cell surface receptor, melanoma cell adhesion molecule (MCAM). Our molecular analyses revealed an important role of ETS translocation variant 4 (ETV4), which is significantly activated in the region downstream of MCAM upon S100A8/A9 stimulation, in breast cancer progression in vitro as well as in vivo. The MCAM-mediated activation of ETV4 induced a mobile phenotype called epithelial-mesenchymal transition (EMT) in cells, since we found that ETV4 transcriptionally upregulate...
Source: Neoplasia - Category: Cancer & Oncology Authors: Tags: Neoplasia Source Type: research
Conclusions This review describes how leukocyte-heparanase can be a double-edged sword in tumor progression; it can enhance tumor immune surveillance and tumor cell clearance, but also promote tumor survival and growth. We also discuss the potential of using heparanase in leukocyte therapies against tumors, and the effects of heparanase inhibitors on tumor progression and immunity. We are just beginning to understand the influence of heparanase on a pro/anti-tumor immune response, and there are still many questions to answer. How do the pro/anti-tumorigenic effects of heparanase differ across different cancer types? Does...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
In this study we adopted an all-in-one method. Primers designed according to the two gRNA sequences and the tracRNA-U6 vector sequences were used to produce a gRNA1-tracRNA-U6-gRNA2 fragment. Then the proper fragment was ligated into the lentiCRISPRv2 vector and verified by sequencing. Lentiviral Packaging and Stable Cell Line Screening The constructed eukaryotic expression vector and gene knockdown vector were transfected into the 293T cells with the packaging plasmids psPAX2 and pMD2.G using Lipofectamine 2000 (Thermo Fisher, Massachusetts, USA). The lentivirus was harvested 48 h after transfection, and the lentivirus ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
This study was carried out in accordance with the recommendations of international guidelines and ethical standards with written informed consent from all subjects. All subjects gave written informed consent in accordance with the Declaration of Helsinki. The protocol was approved by the Institutional Ethics Committee of Kunming General Hospital, China. miRNAs, Plasmids, Transfection, and Irradiation To predict miRNAs with potential binding sites in the 3′UTR of PHLDA2, Targetscan (http://www.targetscan.org/), miRanda (http://www.microrna.org/), and Diana database (http://diana.cslab,ece.nura.gr/) algorithms were u...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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