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Retinoid Metabolism and Retinoic Acid/Retinoid X Receptor Signalling within Cancer and Normal Cells

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: 30 June 2024 | Viewed by 1109

Special Issue Editors


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Guest Editor
School of Medicine, Faculty of Health Sciences and Wellbeing, University of Sunderland, Sunderland SR1 3SD, UK
Interests: retinoic acid receptor isotypes in cancer

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Guest Editor
School of Biomedical Sciences, Institute of Clinical Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
Interests: the use of synthetic retinoids and vitamins D as drug substances; cancer and normal stem cells; anticancer therapies; blood cell development; abnormalities in cancer stem cells
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Special Issue Information

Dear Colleagues,

It has now been more than 35 years since the discovery of specific receptors for the vitamin A derivative, retinoic acid (RA). The receptors for RA comprise two families that function as ligand-dependent transcription factors: the RAR isotypes (α, β, and γ) that are liganded by all-/trans/ RA, and the RXR isotypes (α, β, and γ) that are liganded by 9-/cis/ RA. RXR/RAR bind as obligate heterodimers to cis-acting response elements of RA target genes to generate a high degree of complexity, and play crucial roles in the conduct of normal early development and in controlling the behaviour of cells in the adult organism. Essentially, cancer is a developmental disorder and, therefore, retinoid metabolism and RA signalling are of interest regarding various aspects to the disordered behaviour of cancer cells. The cells that sustain a cancer are cancer stem cells, which, like normal stem cells, generate a hierarchy of cells. Of particular interest is whether there are differences in retinoid metabolism and RA signalling between cancer stem cells and their offspring and their normal counterpart stem cells and their offspring. Differences would allow the targeting of cancer cells to provide new approaches to treating cancer.

The Special Issue will welcome research articles and reviews in the following areas:

  • RA metabolism/biosynthesis and normal cell development
  • RA metabolism/biosynthesis and cancer cells
  • controls on RA biosynthesis enzymes
  • RAR/RXR expression/signalling and normal cell development
  • RAR/RXR expression/signalling and cancer cells
  • controls on RAR/RXR expression
  • RAR/RXR genomic actions
  • RAR/RXR cytoplasmic/non-genomic actions
  • targeting of RA metabolism to treat cancer
  • targeting RAR/RXRs to treat cancer

Dr. Kevin Petrie
Dr. Geoffrey Brown
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 submissions that pass pre-check are 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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Published Papers (1 paper)

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10 pages, 1042 KiB  
Hypothesis
Retinoic Acid Action in Cumulus Cells: Implications for Oocyte Development and In Vitro Fertilization
by Neil Sidell and Augustine Rajakumar
Int. J. Mol. Sci. 2024, 25(3), 1709; https://doi.org/10.3390/ijms25031709 - 30 Jan 2024
Viewed by 752
Abstract
In the field of human in vitro fertilization (IVF), selecting the best oocyte for freezing or embryo for transfer remains an important focus of clinical practice. Although several techniques are and have been used for this goal, results have generally not been favorable [...] Read more.
In the field of human in vitro fertilization (IVF), selecting the best oocyte for freezing or embryo for transfer remains an important focus of clinical practice. Although several techniques are and have been used for this goal, results have generally not been favorable and/or are invasive such that damage to some embryos occurs, resulting in a reduced number of healthy births. Therefore, the search continues for non-invasive oocyte and embryo quality markers that signal the development of high-quality embryos. Multiple studies indicate the important positive effects of retinoic acid (RA) on oocyte maturation and function. We previously showed that a high follicular fluid (FF) RA concentration at the time of oocyte retrieval in IVF protocols was associated with oocytes, giving rise to the highest quality embryos, and that cumulus granulosa cells (CGCs) are the primary source of follicle RA synthesis. Data also demonstrated that connexin-43 (Cx43), the main connexin that forms gap junctions in CGCs, is regulated by RA and that RA induces a rapid increase in gap junction communication. Here, we hypothesize that CGC RA plays a causal role in oocyte competency through its action on Cx43 and, as such, may serve as a biomarker of oocyte competence. Multiple studies have demonstrated the requirement for Cx43 in CGCs for the normal progression of folliculogenesis, and that the increased expression of this connexin is linked to the improved developmental competence of the oocyte. The data have shown that RA can up-regulate gap junction intercellular communication (GJIC) in the cumulus–oocyte complex via a non-genomic mechanism that results in the dephosphorylation of Cx43 and enhanced GJIC. Recognizing the positive role played by gap junctions in CGCs in oocyte development and the regulation of Cx43 by RA, the findings have highlighted the possibility that CGC RA levels may serve as a non-invasive indicator for selecting high-quality oocytes for IVF procedures. In addition, the data suggest that the manipulation of Cx43 with retinoid compounds could provide new pharmacological approaches to improve IVF outcomes in cases of failed implantation, recurrent miscarriage, or in certain diseases that are characterized by reduced fecundity, such as endometriosis. Full article
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