Special Issue "Targeting Signal Transduction Pathways and Non-coding RNAs as Potential Therapy in Cancer and Aging"

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Signaling and Regulated Cell Death".

Deadline for manuscript submissions: 31 May 2021.

Special Issue Editors

Dr. Melchiorre Cervello
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Guest Editor
Institute for Biomedical Research and Innovation (IRIB), Italian National Research Council (CNR), Palermo, Italy
Interests: cancer; hepatocellular carcinoma; targeted therapy; cell signaling; apoptosis; ER stress; nutraceutics
Dr. Maria Rita Emma
Website
Guest Editor
Institute for Biomedical Research and Innovation (IRIB), Italian National Research Council (CNR), Palermo, Italy
Interests: cancer; targeted therapy; signaling pathways; ER stress; pharmacoresistance
Prof. James Albert McCubrey
Website
Guest Editor
Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC, USA
Interests: signaling pathways; chemotherapeutic drugs; nutraceuticals
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

World Health Organization estimates indicate that death from cancer will be the leading cause of death in the world in the next decade, with approximately 22 million new cases per year. It is known that the risk of cancer increases with an individual’s age. If we consider that in the coming decades, the number of people over 65 will double, it is clear that the prevalence of oncological disease will increase in parallel with the aging of the global population.

Cancer is a complex disease in which mutations in the DNA cause the activation of aberrant cellular signals that ultimately affect numerous cellular functions, such as those impacting cell survival, proliferation, and metabolism, as well as communication between different cell types in the cancer microenvironment. Together, these distinctive traits allow tumors to develop, grow, metastasize, and resist therapies.

Aging is also a complex process in which DNA damage and alterations of numerous cellular signals lead to the development of aging-related diseases.

For this Special Issue, we would like to invite original research articles as well as review articles that address the application of cellular and molecular biology to cancer research and aging, from the identification and validation of biomarkers to new therapies and targeted mechanistic studies.

Potential topics include but are not limited to the following:

  • Changes in signaling pathways in cancer and aging;
  • Factors that influence signal transduction in cancer and aging;
  • Roles of microRNAs (miRs) and long noncoding RNAs (lncRNAs) in cancer and aging;
  • New possibilities for targeted therapies in cancer and aging;
  • Optimization of cancer combination therapies.

Dr. Melchiorre Cervello
Dr. Maria Rita Emma
Prof. James Albert McCubrey
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cancer
  • aging
  • signaling pathways
  • targted therapy
  • oncogenes
  • noncoding RNA
  • miR
  • lncRNA
  • tumor suppressor genes

Published Papers (5 papers)

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Research

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Open AccessArticle
Regorafenib Regulates AD Pathology, Neuroinflammation, and Dendritic Spinogenesis in Cells and a Mouse Model of AD
Cells 2020, 9(7), 1655; https://doi.org/10.3390/cells9071655 (registering DOI) - 09 Jul 2020
Abstract
The oral multi-target kinase inhibitor regorafenib, which targets the oncogenic receptor tyrosine kinase (RTK), is an effective therapeutic for patients with advanced gastrointestinal stromal tumors or metastatic colorectal cancer. However, whether regorafenib treatment has beneficial effects on neuroinflammation and Alzheimer’s disease (AD) pathology [...] Read more.
The oral multi-target kinase inhibitor regorafenib, which targets the oncogenic receptor tyrosine kinase (RTK), is an effective therapeutic for patients with advanced gastrointestinal stromal tumors or metastatic colorectal cancer. However, whether regorafenib treatment has beneficial effects on neuroinflammation and Alzheimer’s disease (AD) pathology has not been carefully addressed. Here, we report the regulatory function of regorafenib in neuroinflammatory responses and AD-related pathology in vitro and in vivo. Regorafenib affected AKT signaling to attenuate lipopolysaccharide (LPS)-mediated expression of proinflammatory cytokines in BV2 microglial cells and primary cultured microglia and astrocytes. In addition, regorafenib suppressed LPS-induced neuroinflammatory responses in LPS-injected wild-type mice. In 5x FAD mice (a mouse model of AD), regorafenib ameliorated AD pathology, as evidenced by increased dendritic spine density and decreased Aβ plaque levels, by modulating APP processing and APP processing-associated proteins. Furthermore, regorafenib-injected 5x FAD mice displayed significantly reduced tau phosphorylation at T212 and S214 (AT100) due to the downregulation of glycogen synthase kinase-3 beta (GSK3β) activity. Taken together, our results indicate that regorafenib has beneficial effects on neuroinflammation, AD pathology, and dendritic spine formation in vitro and in vivo. Full article
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Open AccessArticle
Mechanistic Models of Signaling Pathways Reveal the Drug Action Mechanisms behind Gender-Specific Gene Expression for Cancer Treatments
Cells 2020, 9(7), 1579; https://doi.org/10.3390/cells9071579 (registering DOI) - 29 Jun 2020
Abstract
Despite the existence of differences in gene expression across numerous genes between males and females having been known for a long time, these have been mostly ignored in many studies, including drug development and its therapeutic use. In fact, the consequences of such [...] Read more.
Despite the existence of differences in gene expression across numerous genes between males and females having been known for a long time, these have been mostly ignored in many studies, including drug development and its therapeutic use. In fact, the consequences of such differences over the disease mechanisms or the drug action mechanisms are completely unknown. Here we applied mechanistic mathematical models of signaling activity to reveal the ultimate functional consequences that gender-specific gene expression activities have over cell functionality and fate. Moreover, we also used the mechanistic modeling framework to simulate the drug interventions and unravel how drug action mechanisms are affected by gender-specific differential gene expression. Interestingly, some cancers have many biological processes significantly affected by these gender-specific differences (e.g., bladder or head and neck carcinomas), while others (e.g., glioblastoma or rectum cancer) are almost insensitive to them. We found that many of these gender-specific differences affect cancer-specific pathways or in physiological signaling pathways, also involved in cancer origin and development. Finally, mechanistic models have the potential to be used for finding alternative therapeutic interventions on the pathways targeted by the drug, which lead to similar results compensating the downstream consequences of gender-specific differences in gene expression. Full article
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Open AccessArticle
Induction of the Endoplasmic-Reticulum-Stress Response: MicroRNA-34a Targeting of the IRE1α-Branch
Cells 2020, 9(6), 1442; https://doi.org/10.3390/cells9061442 - 10 Jun 2020
Abstract
Neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) are characterized by the accumulation of misfolded proteins in the endoplasmic reticulum (ER) and the unfolded protein response (UPR). Modulating the UPR is one of the major challenges to counteract the development [...] Read more.
Neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) are characterized by the accumulation of misfolded proteins in the endoplasmic reticulum (ER) and the unfolded protein response (UPR). Modulating the UPR is one of the major challenges to counteract the development of neurodegenerative disorders and other diseases with affected UPR. Here, we show that miR-34a-5p directly targets the IRE1α branch of the UPR, including the genes BIP, IRE1α, and XBP1. Upon induction of ER stress in neuronal cells, miR-34a-5p overexpression impacts the resulting UPR via a significant reduction in IRE1α and XBP1s that in turn leads to decreased viability, increased cytotoxicity and caspase activity. The possibility to modify the UPR signaling pathway by a single miRNA that targets central genes of the IRE1α branch offers new perspectives for future therapeutic approaches against neurodegeneration. Full article
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Review

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Open AccessReview
Immuno-Surgical Management of Pancreatic Cancer with Analysis of Cancer Exosomes
Cells 2020, 9(7), 1645; https://doi.org/10.3390/cells9071645 (registering DOI) - 09 Jul 2020
Abstract
Exosomes (EXs), a type of extracellular vesicles secreted from various cells and especially cancer cells, mesenchymal cells, macrophages and other cells in the tumor microenvironment (TME), are involved in biologically malignant behaviors of cancers. Recent studies have revealed that EXs contain microRNAs on [...] Read more.
Exosomes (EXs), a type of extracellular vesicles secreted from various cells and especially cancer cells, mesenchymal cells, macrophages and other cells in the tumor microenvironment (TME), are involved in biologically malignant behaviors of cancers. Recent studies have revealed that EXs contain microRNAs on their inside and express proteins and glycolipids on their outsides, every component of which plays a role in the transmission of genetic and/or epigenetic information in cell-to-cell communications. It is also known that miRNAs are involved in the signal transduction. Thus, EXs may be useful for monitoring the TME of tumor tissues and the invasion and metastasis, processes that are associated with patient survival. Because several solid tumors secrete immune checkpoint proteins, including programmed cell death-ligand 1, the EX-mediated mechanisms are suggested to be potent targets for monitoring patients. Therefore, a companion therapeutic approach against cancer metastasis to distant organs is proposed when surgical removal of the primary tumor is performed. However, EXs and immune checkpoint mechanisms in pancreatic cancer are not fully understood, we provide an update on the recent advances in this field and evidence that EXs will be useful for maximizing patient benefit in precision medicine. Full article
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Open AccessReview
Targeting the JAK/STAT Signaling Pathway Using Phytocompounds for Cancer Prevention and Therapy
Cells 2020, 9(6), 1451; https://doi.org/10.3390/cells9061451 - 11 Jun 2020
Abstract
Cancer is a prevalent cause of mortality around the world. Aberrated activation of Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway promotes tumorigenesis. Natural agents, including phytochemicals, exhibit potent anticancer activities via various mechanisms. However, the therapeutic potency of phytoconstituents [...] Read more.
Cancer is a prevalent cause of mortality around the world. Aberrated activation of Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway promotes tumorigenesis. Natural agents, including phytochemicals, exhibit potent anticancer activities via various mechanisms. However, the therapeutic potency of phytoconstituents as inhibitors of JAK/STAT signaling against cancer has only come into focus in recent days. The current review highlights phytochemicals that can suppress the JAK/STAT pathway in order to impede cancer cell growth. Various databases, such as PubMed, ScienceDirect, Web of Science, SpringerLink, Scopus, and Google Scholar, were searched using relevant keywords. Once the authors were in agreement regarding the suitability of a study, a full-length form of the relevant article was obtained, and the information was gathered and cited. All the complete articles that were incorporated after the literature collection rejection criteria were applied were perused in-depth and material was extracted based on the importance, relevance, and advancement of the apprehending of the JAK/STAT pathway and their relation to phytochemicals. Based on the critical and comprehensive analysis of literature presented in this review, phytochemicals from diverse plant origins exert therapeutic and cancer preventive effects, at least in part, through regulation of the JAK/STAT pathway. Nevertheless, more preclinical and clinical research is necessary to completely comprehend the capability of modulating JAK/STAT signaling to achieve efficient cancer control and treatment. Full article
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