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Biomolecules
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Androgen Receptors in Health and Diseases
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Androgen Receptors in Health and Diseases

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (28 February 2021) | Viewed by 13310

Special Issue Editors

Dr. Shashwat Sharad

E-Mail Website
Guest Editor
Assistant Professor & Staff Scientist-Translational Research, Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences & Walter Reed National Military Medical Center, Henry M. Jackson Foundation, Bethesda, MD 20814, USA
Interests: AR and TGF-β signaling; gene regulation; prostate cancer; epigenetics, epigenomics; DNA methylation, biomarkers, microRNAs in cancer, molecular diagnosis, prognosis, and sub-classification of cancer; natural products as cancer prevention and therapy agents; cancer progression and metastasis; therapeutic resistance in cancer; castrate-resistant prostate cancer, molecular bases of cancer health disparities
Dr. Taduru L. Sreenath

E-Mail Website
Guest Editor
Associate Professor & Associate Director-Translational Research, Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences & Walter Reed National Military Medical Center, Henry M. Jackson Foundation, Bethesda, MD 20814, USA
Interests: androgen receptor; endoplasmic reticulum stress; prostate cancer; tumor heterogeneity; gene functions and molecular mechanisms of cancer initiation; progression and treatment response

Special Issue Information

Dear Colleagues,

This Special Issue of Biomolecules (Impact Factor: 4.694) will cover all aspects of cancer with a special emphasis on androgens and androgen receptor (AR) signaling in health and diseases. The role of androgens and ARs in prostate cancer oncogenesis and disease progression is well established. Their roles in other human malignancies are not clearly understood. The cross-talk with AR and other proteins, such as epidermal growth factor; fibroblast growth factor, IGF1; vascular endothelial growth factor; transforming growth factor-β; growth factor receptors (EGF-R, TrkA) or signaling effectors; protein kinases; and proteins involved in integrin/adhesion pathways, proliferation pathways, triggering invasiveness, and cell cycle progression of prostate cancer cells has also been established. Androgens (testosterone and 5α-dihydrotestosterone) play key roles in the regulation of male development and physiological processes, particularly in the male reproductive system acting through the androgen receptor (AR). The biological effects of androgens are mainly mediated by AR, a master regulator of downstream androgen-dependent signaling pathway networks. Dysregulation or dysfunction of androgen/AR signaling can not only disturb the development of the normal reproductive system, the virilization of the male fetus during embryogenesis, and the development of primary and secondary male sexual characteristics during puberty but also can modulate a wide range of pathological and clinical conditions such as motor neuron disease androgen-insensitive syndrome; motor neuron disease; prostate cancer; spinal bulbar muscular atrophy; male infertility; as well as the initiation, progression, and treatment resistance of prostate cancer.

This Special Issue will initially review the role of AR in advanced prostate cancer, and will then explore the potential role for AR signaling in other epithelial cancers. The articles will focus on the use of novel AR-targeting therapies in castration-resistant prostate cancer and the mechanisms of resistance to novel antiandrogens; the possible role of androgens and AR signaling in breast cancer, bladder cancer, endometrial and ovarian cancers, hepatocellular and pancreatic cancers, and salivary gland cancers; as well as the potential therapeutic implications of using antiandrogen therapies in these nonprostatic malignancies. Research articles on AR signaling are also most welcome. This Special Issue aims to collect a broad range of manuscripts on prostate and other types of cancer (research, clinical, outreach, and public health), which will be considered for inclusion in this Special Issue. We will abridge recent advances in understanding androgen/AR, epigenetic mechanisms of AR action, as well as newly recognized aspects of AR-mediated androgen signaling in both men and women. Additionally, fresh perspectives on the use of animal genetic model systems to develop novel therapeutic AR ligands are welcome. We encourage you to submit original, empirical studies as well as systematic reviews or meta-analyses. Short reports and methodological papers will also be considered. Especially, we encourage the submission of interdisciplinary work and multicountry collaborative research.

Dr. Shashwat Sharad
Dr. Taduru L. Sreenath
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. Biomolecules 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 2700 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

  • androgen
  • androgen receptor (AR)
  • male reproduction
  • female reproduction
  • prostate cancer
  • breast cancer
  • nuclear receptors
  • castration-resistant prostate cancer (CRPC)
  • metastasis
  • AR and coregulatory
  • reproduction
  • other cancer

Published Papers (3 papers)

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Research

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11 pages, 1570 KiB  
Article
Testosterone in Female Depression: A Meta-Analysis and Mendelian Randomization Study
by Dhruba Tara Maharjan, Ali Alamdar Shah Syed, Guan Ning Lin and Weihai Ying
Biomolecules 2021, 11(3), 409; https://doi.org/10.3390/biom11030409 - 10 Mar 2021
Cited by 16 | Viewed by 5339
Abstract
Testosterone’s role in female depression is not well understood, with studies reporting conflicting results. Here, we use meta-analytical and Mendelian randomization techniques to determine whether serum testosterone levels differ between depressed and healthy women and whether such a relationship is casual. Our meta-analysis [...] Read more.
Testosterone’s role in female depression is not well understood, with studies reporting conflicting results. Here, we use meta-analytical and Mendelian randomization techniques to determine whether serum testosterone levels differ between depressed and healthy women and whether such a relationship is casual. Our meta-analysis shows a significant association between absolute serum testosterone levels and female depression, which remains true for the premenopausal group while achieving borderline significance in the postmenopausal group. The results from our Mendelian randomization analysis failed to show any causal relationship between testosterone and depression. Our results show that women with depression do indeed display significantly different serum levels of testosterone. However, the directions of the effect of this relationship are conflicting and may be due to menopausal status. Since our Mendelian randomization analysis was insignificant, the difference in testosterone levels between healthy and depressed women is most likely a manifestation of the disease itself. Further studies could be carried out to leverage this newfound insight into better diagnostic capabilities culminating in early intervention in female depression. Full article
(This article belongs to the Special Issue Androgen Receptors in Health and Diseases)
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Review

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14 pages, 318 KiB  
Review
Current Status and Future Perspectives of Androgen Receptor Inhibition Therapy for Prostate Cancer: A Comprehensive Review
by Tae Jin Kim, Young Hwa Lee and Kyo Chul Koo
Biomolecules 2021, 11(4), 492; https://doi.org/10.3390/biom11040492 - 25 Mar 2021
Cited by 23 | Viewed by 3943
Abstract
The androgen receptor (AR) is one of the main components in the development and progression of prostate cancer (PCa), and treatment strategies are mostly directed toward manipulation of the AR pathway. In the metastatic setting, androgen deprivation therapy (ADT) is the foundation of [...] Read more.
The androgen receptor (AR) is one of the main components in the development and progression of prostate cancer (PCa), and treatment strategies are mostly directed toward manipulation of the AR pathway. In the metastatic setting, androgen deprivation therapy (ADT) is the foundation of treatment in patients with hormone-sensitive prostate cancer (HSPC). However, treatment response is short-lived, and the majority of patients ultimately progress to castration-resistant prostate cancer (CRPC). Surmountable data from clinical trials have shown that the maintenance of AR signaling in the castration environment is accountable for disease progression. Study results indicate multiple factors and survival pathways involved in PCa. Based on these findings, the alternative molecular pathways involved in PCa progression can be manipulated to improve current regimens and develop novel treatment modalities in the management of CRPC. In this review, the interaction between AR signaling and other molecular pathways involved in tumor pathogenesis and its clinical implications in metastasis and advanced disease will be discussed, along with a thorough overview of current and ongoing novel treatments for AR signaling inhibition. Full article
(This article belongs to the Special Issue Androgen Receptors in Health and Diseases)
13 pages, 2514 KiB  
Review
PMEPA1 Gene Isoforms: A Potential Biomarker and Therapeutic Target in Prostate Cancer
by Shashwat Sharad, Albert Dobi, Shiv Srivastava, Alagarsamy Srinivasan and Hua Li
Biomolecules 2020, 10(9), 1221; https://doi.org/10.3390/biom10091221 - 22 Aug 2020
Cited by 11 | Viewed by 3389
Abstract
The identification of prostate transmembrane protein androgen induced 1 (PMEPA1), an androgen responsive gene, came initially from the studies of androgen regulatory gene networks in prostate cancer. It was soon followed by the documentation of the expression and functional analysis of [...] Read more.
The identification of prostate transmembrane protein androgen induced 1 (PMEPA1), an androgen responsive gene, came initially from the studies of androgen regulatory gene networks in prostate cancer. It was soon followed by the documentation of the expression and functional analysis of transmembrane prostate androgen-induced protein (TMEPAI)/PMEPA1 in other solid tumors including renal, colon, breast, lung, and ovarian cancers. Further elucidation of PMEPA1 gene expression and sequence analysis revealed the presence of five isoforms with distinct extracellular domains (isoforms a, b, c, d, and e). Notably, the predicted amino acid sequences of PMEPA1 isoforms show differences at the N-termini, a conserved membrane spanning and cytoplasmic domains. PMEPA1 serves as an essential regulator of multiple signaling pathways including androgen and TGF-β signaling in solid tumors. Structure-function studies indicate that specific motifs present in the cytoplasmic domain (PY, SIM, SH3, and WW binding domains) are utilized to mediate isoform-specific functions through interactions with other proteins. The understanding of the “division of labor” paradigm exhibited by PMEPA1 isoforms further expands our knowledge of gene’s multiple functions in tumorigenesis. In this review, we aim to summarize the most recent advances in understanding of PMEPA1 isoform-specific functions and their associations with prostate cancer progression, highlighting the potentials as biomarker and therapeutic target in prostate cancer. Full article
(This article belongs to the Special Issue Androgen Receptors in Health and Diseases)
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