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Cells
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Ovary and Brain
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Ovary and Brain

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Intracellular and Plasma Membranes".

Deadline for manuscript submissions: closed (5 March 2022) | Viewed by 39452

Special Issue Editors

Dr. Ilana Chefetz

E-Mail Website
Guest Editor
Hormel Institute, Masonic Cancer Center, University of Minnesota, Austin, MN 55912-3679, USA
Interests: cell death; ovarian cancer; cancer stem cells; cell programmed necrosis (necroptosis); chemoresistance
Special Issues, Collections and Topics in MDPI journals
Dr. Martina Bazzaro

E-Mail Website1 Website2
Guest Editor
Masonic Cancer Center and Department of Obstetrics, Gynecology and Women’s Health, University of Minnesota, Minneapolis, MN 55455, USA
Interests: ovarian cancer; microtubules; regulation of microtubule dynamics; microtubule-associated proteins; mitochondrial metabolism; neurodegeneration

Special Issue Information

Dear colleagues,

For the longest time, cancer and neurodegenerative diseases have been considered to be at opposite ends of the spectrum of human diseases—cancer is characterized by highly dividing cells that resist death while neurodegenerative diseases are associated with the death of post-mitotic cells. However, emerging genetic and cell biology studies show multiple common pathways in cancer and neurodegeneration. This includes pathways and proteins involved in the regulation of both microtubule and mitochondrial dynamics. For example, the microtubule-targeting drug paclitaxel is an established anti-cancer approach, including for ovarian cancer, while the stabilization of neuronal MTs can attenuate neurodegeneration in mouse models of Alzheimer disease (AD) and other neurodegenerative disease caused by or associated with the loss of microtubule mass. Furthermore, mitochondrial dysfunction is a key pathological process in several neurodegenerative diseases, as well as in cancers. Given the common pathways regulating brain and human cancers (including ovarian cancer), our understanding of the mechanisms that regulate them is of significant importance for both cancer and neurodegeneration.

Dr. Ilana Chefetz
Dr. Martina Bazzaro
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. Cells is an international peer-reviewed open access semimonthly 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

  • ovarian cancer
  • brain
  • innervation
  • neurotransmitter modulator
  • microtubules
  • cellular polarization
  • reproduction
  • metabolism
  • kinase activity
  • neurodegeneration

Related Special Issue

Published Papers (8 papers)

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Editorial

Jump to: Research, Review

8 pages, 238 KiB  
Editorial
The Ovary–Brain Connection
by Abdelrahman Yousif, Ahmed Ebeid, Balint Kacsoh, Martina Bazzaro and Ilana Chefetz
Cells 2024, 13(1), 94; https://doi.org/10.3390/cells13010094 - 2 Jan 2024
Viewed by 1619
Abstract
The brain and the ovaries are in a state of continuous communication [...] Full article
(This article belongs to the Special Issue Ovary and Brain)

Research

Jump to: Editorial, Review

17 pages, 4338 KiB  
Article
Intra-Tumoral Nerve-Tracing in a Novel Syngeneic Model of High-Grade Serous Ovarian Carcinoma
by Jeffrey L. Barr, Allison Kruse, Anthony C. Restaino, Natalia Tulina, Sarah Stuckelberger, Samuel J. Vermeer, Caitlin S. Williamson, Daniel W. Vermeer, Marianna Madeo, Jillian Stamp, Maria Bell, Mark Morgan, Ju-Yoon Yoon, Marilyn A. Mitchell, Anna Budina, Dalia K. Omran, Lauren E. Schwartz, Ronny Drapkin and Paola D. Vermeer
Cells 2021, 10(12), 3491; https://doi.org/10.3390/cells10123491 - 10 Dec 2021
Cited by 8 | Viewed by 4373
Abstract
Dense tumor innervation is associated with enhanced cancer progression and poor prognosis. We observed innervation in breast, prostate, pancreatic, lung, liver, ovarian, and colon cancers. Defining innervation in high-grade serous ovarian carcinoma (HGSOC) was a focus since sensory innervation was observed whereas the [...] Read more.
Dense tumor innervation is associated with enhanced cancer progression and poor prognosis. We observed innervation in breast, prostate, pancreatic, lung, liver, ovarian, and colon cancers. Defining innervation in high-grade serous ovarian carcinoma (HGSOC) was a focus since sensory innervation was observed whereas the normal tissue contains predominantly sympathetic input. The origin, specific nerve type, and the mechanisms promoting innervation and driving nerve-cancer cell communications in ovarian cancer remain largely unknown. The technique of neuro-tracing enhances the study of tumor innervation by offering a means for identification and mapping of nerve sources that may directly and indirectly affect the tumor microenvironment. Here, we establish a murine model of HGSOC and utilize image-guided microinjections of retrograde neuro-tracer to label tumor-infiltrating peripheral neurons, mapping their source and circuitry. We show that regional sensory neurons innervate HGSOC tumors. Interestingly, the axons within the tumor trace back to local dorsal root ganglia as well as jugular–nodose ganglia. Further manipulations of these tumor projecting neurons may define the neuronal contributions in tumor growth, invasion, metastasis, and responses to therapeutics. Full article
(This article belongs to the Special Issue Ovary and Brain)
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13 pages, 6601 KiB  
Article
UNC-45A Is Highly Expressed in the Proliferative Cells of the Mouse Genital Tract and in the Microtubule-Rich Areas of the Mouse Nervous System
by Valentino Clemente, Asumi Hoshino, Joyce Meints, Mihir Shetty, Tim Starr, Michael Lee and Martina Bazzaro
Cells 2021, 10(7), 1604; https://doi.org/10.3390/cells10071604 - 26 Jun 2021
Cited by 3 | Viewed by 2278
Abstract
UNC-45A (Protein unc-45 homolog A) is a cytoskeletal-associated protein with a dual and non-mutually exclusive role as a regulator of the actomyosin system and a Microtubule (MT)-destabilizing protein, which is overexpressed in human cancers including in ovarian cancer patients resistant to the MT-stabilizing [...] Read more.
UNC-45A (Protein unc-45 homolog A) is a cytoskeletal-associated protein with a dual and non-mutually exclusive role as a regulator of the actomyosin system and a Microtubule (MT)-destabilizing protein, which is overexpressed in human cancers including in ovarian cancer patients resistant to the MT-stabilizing drug paclitaxel. Mapping of UNC-45A in the mouse upper genital tract and central nervous system reveals its enrichment not only in highly proliferating and prone to remodeling cells, but also in microtubule-rich areas, of the ovaries and the nervous system, respectively. In both apparatuses, UNC-45A is also abundantly expressed in the ciliated epithelium. As regulators of actomyosin contractility and MT stability are essential for the physiopathology of the female reproductive tract and of neuronal development, our findings suggest that UNC-45A may have a role in ovarian cancer initiation and development as well as in neurodegeneration. Full article
(This article belongs to the Special Issue Ovary and Brain)
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Review

Jump to: Editorial, Research

19 pages, 1174 KiB  
Review
H3K27me3 in Diffuse Midline Glioma and Epithelial Ovarian Cancer: Opposing Epigenetic Changes Leading to the Same Poor Outcomes
by Charles A. Day, Edward H. Hinchcliffe and James P. Robinson
Cells 2022, 11(21), 3376; https://doi.org/10.3390/cells11213376 - 26 Oct 2022
Cited by 12 | Viewed by 3046
Abstract
Histone post-translational modifications modulate gene expression through epigenetic gene regulation. The core histone H3 family members, H3.1, H3.2, and H3.3, play a central role in epigenetics. H3 histones can acquire many post-translational modifications, including the trimethylation of H3K27 (H3K27me3), which represses transcription. Triple [...] Read more.
Histone post-translational modifications modulate gene expression through epigenetic gene regulation. The core histone H3 family members, H3.1, H3.2, and H3.3, play a central role in epigenetics. H3 histones can acquire many post-translational modifications, including the trimethylation of H3K27 (H3K27me3), which represses transcription. Triple methylation of H3K27 is performed by the histone methyltransferase Enhancer of Zeste Homologue 2 (EZH2), a component of the Polycomb Repressive Complex 2. Both global increases and decreases in H3K27me3 have been implicated in a wide range of cancer types. Here, we explore how opposing changes in H3K27me3 contribute to cancer by highlighting its role in two vastly different cancer types; (1) a form of glioma known as diffuse midline glioma H3K27-altered and (2) epithelial ovarian cancer. These two cancers vary widely in the age of onset, sex, associated mutations, and cell and organ type. However, both diffuse midline glioma and ovarian cancer have dysregulation of H3K27 methylation, triggering changes to the cancer cell transcriptome. In diffuse midline glioma, the loss of H3K27 methylation is a primary driving factor in tumorigenesis that promotes glial cell stemness and silences tumor suppressor genes. Conversely, hypermethylation of H3K27 occurs in late-stage epithelial ovarian cancer, which promotes tumor vascularization and tumor cell migration. By using each cancer type as a case study, this review emphasizes the importance of H3K27me3 in cancer while demonstrating that the mechanisms of histone H3 modification and subsequent gene expression changes are not a one-size-fits-all across cancer types. Full article
(This article belongs to the Special Issue Ovary and Brain)
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25 pages, 1245 KiB  
Review
Role of Estrogens in Menstrual Migraine
by Rossella E. Nappi, Lara Tiranini, Simona Sacco, Eleonora De Matteis, Roberto De Icco and Cristina Tassorelli
Cells 2022, 11(8), 1355; https://doi.org/10.3390/cells11081355 - 15 Apr 2022
Cited by 30 | Viewed by 9783
Abstract
Migraine is a major neurological disorder affecting one in nine adults worldwide with a significant impact on health care and socioeconomic systems. Migraine is more prevalent in women than in men, with 17% of all women meeting the diagnostic criteria for migraine. In [...] Read more.
Migraine is a major neurological disorder affecting one in nine adults worldwide with a significant impact on health care and socioeconomic systems. Migraine is more prevalent in women than in men, with 17% of all women meeting the diagnostic criteria for migraine. In women, the frequency of migraine attacks shows variations over the menstrual cycle and pregnancy, and the use of combined hormonal contraception (CHC) or hormone replacement therapy (HRT) can unveil or modify migraine disease. In the general population, 18–25% of female migraineurs display a menstrual association of their headache. Here we present an overview on the evidence supporting the role of reproductive hormones, in particular estrogens, in the pathophysiology of migraine. We also analyze the efficacy and safety of prescribing exogenous estrogens as a potential treatment for menstrual-related migraine. Finally, we point to controversial issues and future research areas in the field of reproductive hormones and migraine. Full article
(This article belongs to the Special Issue Ovary and Brain)
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12 pages, 471 KiB  
Review
Biomarkers of Central Nervous System Involvement from Epithelial Ovarian Cancer
by Giulia Scotto, Fulvio Borella, Margherita Turinetto, Valentina Tuninetti, Anna A. Valsecchi, Gaia Giannone, Stefano Cosma, Chiara Benedetto and Giorgio Valabrega
Cells 2021, 10(12), 3408; https://doi.org/10.3390/cells10123408 - 3 Dec 2021
Cited by 4 | Viewed by 2100
Abstract
Epithelial ovarian cancer (EOC) is the leading cause of death among women affected by gynaecological malignancies. Most patients show advanced disease at diagnosis (FIGO stage III-IV) and, despite the introduction of new therapeutic options, most women experience relapses. In most cases, recurrence is [...] Read more.
Epithelial ovarian cancer (EOC) is the leading cause of death among women affected by gynaecological malignancies. Most patients show advanced disease at diagnosis (FIGO stage III-IV) and, despite the introduction of new therapeutic options, most women experience relapses. In most cases, recurrence is abdominal-pelvic; however, EOC can occasionally metastasize to distant organs, including the central nervous system. The incidence of brain metastases (BMs) from EOC is low, but it has grown over time; currently, there are no follow-up strategies available. In the last decade, a few biomarkers able to predict the risk of developing BMs from OC or as potential therapeutic targets have been investigated by several authors; to date, none have entered clinical practice. The purpose of this review is to offer a summary on the role of the most relevant predictors of central nervous system (CNS) involvement (hormone receptors; BRCA; MRD1; PD-1/PD-L1) and to highlight possible therapeutic strategies for the management of metastatic brain disease in EOC Full article
(This article belongs to the Special Issue Ovary and Brain)
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17 pages, 3143 KiB  
Review
NUAK Kinases: Brain–Ovary Axis
by Ester Molina, Linda Hong and Ilana Chefetz
Cells 2021, 10(10), 2760; https://doi.org/10.3390/cells10102760 - 15 Oct 2021
Cited by 7 | Viewed by 3294
Abstract
Liver kinase B (LKB1) and adenosine monophosphate (AMP)-activated protein kinase (AMPK) are two major kinases that regulate cellular metabolism by acting as adenosine triphosphate (ATP) sensors. During starvation conditions, LKB1 and AMPK activate different downstream pathways to increase ATP production, while decreasing ATP [...] Read more.
Liver kinase B (LKB1) and adenosine monophosphate (AMP)-activated protein kinase (AMPK) are two major kinases that regulate cellular metabolism by acting as adenosine triphosphate (ATP) sensors. During starvation conditions, LKB1 and AMPK activate different downstream pathways to increase ATP production, while decreasing ATP consumption, which abrogates cellular proliferation and cell death. Initially, LKB1 was considered to be a tumor suppressor due to its loss of expression in various tumor types. Additional studies revealed amplifications in LKB1 and AMPK kinases in several cancers, suggesting a role in tumor progression. The AMPK-related proteins were described almost 20 years ago as a group of key kinases involved in the regulation of cellular metabolism. As LKB1-downstream targets, AMPK-related proteins were also initially considered to function as tumor suppressors. However, further research demonstrated that AMPK-related kinases play a major role not only in cellular physiology but also in tumor development. Furthermore, aside from their role as regulators of metabolism, additional functions have been described for these proteins, including roles in the cell cycle, cell migration, and cell death. In this review, we aim to highlight the major role of AMPK-related proteins beyond their functions in cellular metabolism, focusing on cancer progression based on their role in cell migration, invasion, and cell survival. Additionally, we describe two main AMPK-related kinases, Novel (nua) kinase family 1 (NUAK1) and 2 (NUAK2), which have been understudied, but play a major role in cellular physiology and tumor development. Full article
(This article belongs to the Special Issue Ovary and Brain)
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16 pages, 2473 KiB  
Review
The Intersection of Purine and Mitochondrial Metabolism in Cancer
by Humberto De Vitto, Danushka B. Arachchige, Brian C. Richardson and Jarrod B. French
Cells 2021, 10(10), 2603; https://doi.org/10.3390/cells10102603 - 30 Sep 2021
Cited by 31 | Viewed by 9565
Abstract
Nucleotides are essential to cell growth and survival, providing cells with building blocks for DNA and RNA, energy carriers, and cofactors. Mitochondria have a critical role in the production of intracellular ATP and participate in the generation of intermediates necessary for biosynthesis of [...] Read more.
Nucleotides are essential to cell growth and survival, providing cells with building blocks for DNA and RNA, energy carriers, and cofactors. Mitochondria have a critical role in the production of intracellular ATP and participate in the generation of intermediates necessary for biosynthesis of macromolecules such as purines and pyrimidines. In this review, we highlight the role of purine and mitochondrial metabolism in cancer and how their intersection influences cancer progression, especially in ovarian cancer. Additionally, we address the importance of metabolic rewiring in cancer and how the evolving landscape of purine synthesis and mitochondria inhibitors can be potentially exploited for cancer treatment. Full article
(This article belongs to the Special Issue Ovary and Brain)
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