The Multifunctional Protein p62 and Its Mechanistic Roles in Cancers.

The Multifunctional Protein p62 and Its Mechanistic Roles in Cancers. Curr Cancer Drug Targets. 2018 Oct 16;: Authors: Ning S, Wang L Abstract The multifunctional signaling hub p62 is well recognized as ubiquitin sensor and selective autophagy adaptor under myriad stress conditions including cancer. As a ubiquitin sensor, p62 promotes NFκB activation by facilitating TRAF6 ubiquitination and aggregation. As a selective autophagy receptor, p62 links ubiquitinated substrates including p62 itself for lysosome-mediated degradation. p62 plays crucial roles in myriad cellular processes including DNA damage response, aging/senescence, infection and immunity, chronic inflammation, and cancerogenesis, dependent on or independent of autophagy. Targeting p62-mediated autophagy may represent a promising strategy for clinical interventions of different cancers. In this review, we summarize the transcriptional and post-translational regulation of p62, and its mechanistic roles in cancers, with the emphasis on its roles in regulation of DNA damage response and its connection to the cGAS-STING-mediated antitumor immune response, which is promising for cancer vaccine design. PMID: 30332964 [PubMed - as supplied by publisher]
Source: Current Cancer Drug Targets - Category: Cancer & Oncology Authors: Tags: Curr Cancer Drug Targets Source Type: research

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AbstractThe expression of antigens that are recognized by self-reactive T cells is essential for immune-mediated tumor rejection by immune checkpoint blockade (ICB) therapy. Growing evidence suggests that mutation-associated neoantigens drive ICB responses in tumors with high mutational burden. In most patients, only a few of the mutations in the cancer exome that are predicted to be immunogenic are recognized by T cells. One factor that limits this recognition is the level of expression of the mutated gene product in cancer cells. Substantial preclinical data show that radiation can convert the irradiated tumor into a sit...
Source: Genome Medicine - Category: Genetics & Stem Cells Source Type: research
Marjolein Schluck1,2, Roel Hammink1,2, Carl G. Figdor1,2,3, Martijn Verdoes1,3*† and Jorieke Weiden1,2,3*† 1Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands 2Division of Immunotherapy, Oncode Institute, Radboud University Medical Center, Nijmegen, Netherlands 3Institute for Chemical Immunology, Nijmegen, Netherlands Traditional tumor vaccination approaches mostly focus on activating dendritic cells (DCs) by providing them with a source of tumor antigens and/or adjuvants, which in turn activate tumor-reactive T c...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
María Maximina B. Moreno-Altamirano1*, Simon E. Kolstoe2 and Francisco Javier Sánchez-García1* 1Laboratorio de Inmunorregulación, Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City, Mexico 2School of Health Sciences, University of Portsmouth, Portsmouth, United Kingdom Over the last decade, there has been significant advances in the understanding of the cross-talk between metabolism and immune responses. It is now evident that immune cell effector function strongly depends on the metabolic pathway in w...
Source: Frontiers in cellular and infection microbiology - Category: Microbiology Source Type: research
In this study, taking advantage of dsDNA and dsRNA viral mimics, we investigated the global transcriptome changes after the antiviral immunity activation in mouse embryonic fibroblasts. Results from our data identified a positive feedback up-regulation of sensors (e.g., Tlr2, Tlr3, Ddx58, cGAS), transducers (e.g., Traf2, Tbk1) and transcription factors (e.g., Irf7, Jun, Stat1, Stat2) in multiple pathways involved in detecting viral or microbial infections upon viral mimic stimulation. A group of genes involved in DNA damage response and DNA repair such as Parp9, Dtx3l, Rad52 were also up-regulated, implying the involvement...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
In this study, several biopsies from a patient-derived primary renal-cell carcinoma were analyzed by whole-exome sequencing and aligned to healthy tissue. Next to several shared mutations between different subclones, ca. 23% of the mutations were only found in specific regions of the tumor. Strikingly, a single biopsy of that same tumor only covered around 55% of the total mutational diversity, underlining the need for multi-region sampling. Tracing the order of mutations in different subclones revealed that they develop in a branching fashion from the primary tumor clone, harboring the driver mutation, rather than in a li...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
In conclusion, we hope that this review brings about a new and more in-depth understanding of the part that Leishmania exosomes and various infectious agents play in the context of host-parasite interactions, with a particular focus on the establishment of infection. Future research in this field of investigations is critical for the development of new vaccine and diagnostic tools. Author Contributions The first draft was done by MO. AF and GD added new information. Funding Research in MO laboratory is supported by the Canadian Institute of Health Research (grant number: PJT-159765) and the Natural Sciences and Enginee...
Source: Frontiers in cellular and infection microbiology - Category: Microbiology Source Type: research
In conclusion, the DHAV-1 CH60 strain may inhibit the expression of IFNα by increasing the SOCS3 protein and SOCS3 can in turn decrease STAT1 and STAT3 mRNA levels, thereby inhibiting the antiviral protein MX1 and ultimately promoting viral proliferation, indirectly assisting in viral adaptation in chicken embryos. Introduction Duck hepatitis A virus type 1 (DHAV-1) is one of the most lethal pathogens for ducks, especially ducklings
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
AbstractCancer vaccines and oncolytic immunotherapy are promising treatment strategies with potential to provide greater clinical benefit to patients with advanced-stage cancer. In particular, recombinant vaccinia viruses (VV) hold great promise as interventional agents. In this article, we first summarize the current understanding of virus biology and viral genes involved in host-virus interactions to further improve the utility of these agents in therapeutic applications. We then discuss recent findings from basic and clinical studies using VV as cancer vaccines and oncolytic immunotherapies. Despite encouraging results ...
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
[WHO] As she felt the cold sting of the needle enter her arm, Alice winced in fear more than pain- understandable as she is only 10. However, a moment of pain could save her from the leading cause of cancer death among women in Africa: cervical cancer. She is receiving a vaccine against human papilloma virus (HPV), the main gateway agent in cervical cancer.
Source: AllAfrica News: Health and Medicine - Category: African Health Source Type: news
Abstract Cyclic di-GMP (CDG) was applied to MUC1 glycopeptide-based cancer vaccines with physical mixing and built-in (at 2'-OH of CDG) strategies for activating the STING pathway. CDG in both strategies behaved as a potent immunostimulant and contributed to high titers of IgG antibodies and the expression of multiple cytokines. PMID: 30101273 [PubMed - as supplied by publisher]
Source: Chemical Communications - Category: Chemistry Authors: Tags: Chem Commun (Camb) Source Type: research
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