Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
9.9
5.1
Journals
Cells
Special Issues
Hormone Dependent Cancers: Molecular Mechanisms and Therapeutical Implications
share announcement

Hormone Dependent Cancers: Molecular Mechanisms and Therapeutical Implications

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Pathology".

Deadline for manuscript submissions: closed (1 April 2021) | Viewed by 38543

Special Issue Editor

Dr. Günter Emons

E-Mail Website
Guest Editor
Universität Göttingen, Gottingen, Germany

Special Issue Information

Hormone-dependent cancers of the breast and prostate are the most common cancers in women and men, respectively. Endogenous and exogenous steroids as well as proteo- and peptide hormones play essential roles in their development and progression. Pharmacological manipulations of these endocrine mechanisms are a cornerstone of treatment of these tumours, which eventually develop resistance to endocrine therapy.

Recently, knowledge of different estrogen, progestin, and androgen receptors, both nuclear and membrane-bound, has markedly improved. The role of mutations of the receptors, and interactions with other hormones including prolactin or growth factor systems, e.g., insulin-like growths factor or the RANK/RANKL system, have become evident. Mutations of transcription factors of sex steroids and changes in their metabolism have a relevant impact on tumour development and resistance to endocrine therapy.

Other typical and frequent hormone-dependent malignancies are endometrial and ovarian cancers. Testicular and certain thyroid cancers are relatively rare, but also considered to be hormone-dependent. Colorectal, lung, and liver cancer, as well as meningioma, are considered to be hormone-related.

Some environmental chemicals with estrogenic activity, so-called endocrine disruptors, may interfere with endocrine regulatory systems already during intrauterine life and thus contribute to the development of the above tumours. 

Dr. Günter Emons
Guest Editor

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

  • Breast cancer
  • Prostate cancer
  • Endometrial cancer
  • Ovarian cancer
  • Testicular cancer
  • Thyroid cancer
  • Meningioma
  • Colorectal cancer
  • Lung cancer
  • Liver cancer

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue polices can be found here.

Published Papers (9 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Editorial

Jump to: Research, Review

2 pages, 176 KiB  
Editorial
Hormone-Dependent Cancers: Molecular Mechanisms and Therapeutical Implications
by Günter Emons
Cells 2023, 12(1), 110; https://doi.org/10.3390/cells12010110 - 28 Dec 2022
Cited by 5 | Viewed by 1824
Abstract
Hormone-dependent cancers of the breast and prostate are the most common cancers in women and men, respectively [...] Full article
(This article belongs to the Special Issue Hormone Dependent Cancers: Molecular Mechanisms and Therapeutical Implications)

Research

Jump to: Editorial, Review

11 pages, 1088 KiB  
Communication
Human Chorionic Gonadotropin-Mediated Induction of Breast Cancer Cell Proliferation and Differentiation
by Ilaria Dando, Cristian Andres Carmona-Carmona and Nicola Zampieri
Cells 2021, 10(2), 264; https://doi.org/10.3390/cells10020264 - 29 Jan 2021
Cited by 6 | Viewed by 2946
Abstract
Human chorionic gonadotropin (hCG) is a hormone that specifically binds to luteinizing hormone receptor (LHR) and exerts several roles, including the support of pregnancy and fetal gonadal steroidogenesis. Since hCG is also expressed by some tumor types, like breast cancer, many efforts have [...] Read more.
Human chorionic gonadotropin (hCG) is a hormone that specifically binds to luteinizing hormone receptor (LHR) and exerts several roles, including the support of pregnancy and fetal gonadal steroidogenesis. Since hCG is also expressed by some tumor types, like breast cancer, many efforts have been made to study its role in neoplesia, with some studies showing a cancer-supportive role and others showing a cancer-protective role. A critical examination of the literature highlighted that the in vitro effect of hCG has been tested in the presence of fetal serum, which contains other gonadotropins, in the culture medium. Thus, we hypothesized that the use of serum in the cell culture medium might influence the cell response to the hCG treatment due to the presence of other hormones. Thus, we analyzed the in vitro effect of highly purified hCG on cell proliferation and the activation of the down-stream signal transduction pathway in three breast cancer cell lines, particularly focusing on MCF7, cultured in serum-deprived conditions. Our data show that hCG increases cell proliferation and activates the down-stream target Akt, together with a decrease of the LHR mRNA expression level. Finally, we also tested the differentiation capacity of hCG on MCF7 cancer stem cells (CSCs) and show that it favors the proliferation and differentiation of these cells, thus suggesting that hCG also renders cells more able to colonize and invade the organs. Full article
(This article belongs to the Special Issue Hormone Dependent Cancers: Molecular Mechanisms and Therapeutical Implications)
►▼ Show Figures

Figure 1

15 pages, 1613 KiB  
Article
Influence of ARHGAP29 on the Invasion of Mesenchymal-Transformed Breast Cancer Cells
by Katharina Kolb, Johanna Hellinger, Maike Kansy, Florian Wegwitz, Gerd Bauerschmitz, Günter Emons and Carsten Gründker
Cells 2020, 9(12), 2616; https://doi.org/10.3390/cells9122616 - 5 Dec 2020
Cited by 5 | Viewed by 3214
Abstract
Aggressive and mesenchymal-transformed breast cancer cells show high expression levels of Rho GTPase activating protein 29 (ARHGAP29), a negative regulator of RhoA. ARHGAP29 was the only one of 32 GTPase-activating enzymes whose expression significantly increased after the induction of mesenchymal transformation in breast [...] Read more.
Aggressive and mesenchymal-transformed breast cancer cells show high expression levels of Rho GTPase activating protein 29 (ARHGAP29), a negative regulator of RhoA. ARHGAP29 was the only one of 32 GTPase-activating enzymes whose expression significantly increased after the induction of mesenchymal transformation in breast cancer cells. Therefore, we investigated the influence of ARHGAP29 on the invasiveness of aggressive and mesenchymal-transformed breast cancer cells. After knock-down of ARHGAP29 using siRNA, invasion of HCC1806, MCF-7-EMT, and T-47D-EMT breast cancer cells was significantly reduced. This could be explained by reduced inhibition of RhoA and a consequent increase in stress fiber formation. Proliferation of the breast cancer cell line T-47D-EMT was slightly increased by reduced expression of ARHGAP29, whereas that of HCC1806 and MCF-7-EMT significantly increased. Using interaction analyses we found that AKT1 is a possible interaction partner of ARHGAP29. Therefore, the expression of AKT1 after siRNA knock-down of ARHGAP29 was tested. Reduced ARHGAP29 expression was accompanied by significantly reduced AKT1 expression. However, the ratio of active pAKT1 to total AKT1 remained unchanged or was significantly increased after ARHGAP29 knock-down. Our results show that ARHGAP29 could be an important factor in the invasion of aggressive and mesenchymal-transformed breast cancer cells. Further research is required to fully understand the underlying mechanisms. Full article
(This article belongs to the Special Issue Hormone Dependent Cancers: Molecular Mechanisms and Therapeutical Implications)
►▼ Show Figures

Figure 1

20 pages, 3583 KiB  
Article
Cholesterol as an Endogenous Ligand of ERRα Promotes ERRα-Mediated Cellular Proliferation and Metabolic Target Gene Expression in Breast Cancer Cells
by Faegheh Ghanbari, Sylvie Mader and Anie Philip
Cells 2020, 9(8), 1765; https://doi.org/10.3390/cells9081765 - 23 Jul 2020
Cited by 22 | Viewed by 3459
Abstract
Breast cancer is the 2nd leading cause of cancer-related death among women. Increased risk of breast cancer has been associated with high dietary cholesterol intake. However, the underlying mechanisms are not known. The nuclear receptor, estrogen-related receptor alpha (ERRα), plays an important role [...] Read more.
Breast cancer is the 2nd leading cause of cancer-related death among women. Increased risk of breast cancer has been associated with high dietary cholesterol intake. However, the underlying mechanisms are not known. The nuclear receptor, estrogen-related receptor alpha (ERRα), plays an important role in breast cancer cell metabolism, and its overexpression has been linked to poor survival. Here we identified cholesterol as an endogenous ligand of ERRα by purification from human pregnancy serum using a GST-ERRα affinity column and liquid chromatography-tandem mass spectrometry (LC-MS/MS). We show that cholesterol interacts with ERRα and induces its transcriptional activity in estrogen receptor positive (ER+) and triple negative breast cancer (TNBC) cells. In addition, we show that cholesterol enhances ERRα-PGC-1α interaction, induces ERRα expression itself, augments several metabolic target genes of ERRα, and increases cell proliferation and migration in both ER+ and TNBC cells. Furthermore, the stimulatory effect of cholesterol on metabolic gene expression, cell proliferation, and migration requires the ERRα pathway. These findings provide a mechanistic explanation for the increased breast cancer risk associated with high dietary cholesterol and possibly the pro-survival effect of statins in breast cancer patients, highlighting the clinical relevance of lowering cholesterol levels in breast cancer patients overexpressing ERRα. Full article
(This article belongs to the Special Issue Hormone Dependent Cancers: Molecular Mechanisms and Therapeutical Implications)
►▼ Show Figures

Figure 1

Review

Jump to: Editorial, Research

26 pages, 1371 KiB  
Review
Dissecting the Hormonal Signaling Landscape in Castration-Resistant Prostate Cancer
by Fabrizio Fontana and Patrizia Limonta
Cells 2021, 10(5), 1133; https://doi.org/10.3390/cells10051133 - 7 May 2021
Cited by 14 | Viewed by 3350
Abstract
Understanding the molecular mechanisms underlying prostate cancer (PCa) progression towards its most aggressive, castration-resistant (CRPC) stage is urgently needed to improve the therapeutic options for this almost incurable pathology. Interestingly, CRPC is known to be characterized by a peculiar hormonal landscape. It is [...] Read more.
Understanding the molecular mechanisms underlying prostate cancer (PCa) progression towards its most aggressive, castration-resistant (CRPC) stage is urgently needed to improve the therapeutic options for this almost incurable pathology. Interestingly, CRPC is known to be characterized by a peculiar hormonal landscape. It is now well established that the androgen/androgen receptor (AR) axis is still active in CRPC cells. The persistent activity of this axis in PCa progression has been shown to be related to different mechanisms, such as intratumoral androgen synthesis, AR amplification and mutations, AR mRNA alternative splicing, increased expression/activity of AR-related transcription factors and coregulators. The hypothalamic gonadotropin-releasing hormone (GnRH), by binding to its specific receptors (GnRH-Rs) at the pituitary level, plays a pivotal role in the regulation of the reproductive functions. GnRH and GnRH-R are also expressed in different types of tumors, including PCa. Specifically, it has been demonstrated that, in CRPC cells, the activation of GnRH-Rs is associated with a significant antiproliferative/proapoptotic, antimetastatic and antiangiogenic activity. This antitumor activity is mainly mediated by the GnRH-R-associated Gαi/cAMP signaling pathway. In this review, we dissect the molecular mechanisms underlying the role of the androgen/AR and GnRH/GnRH-R axes in CRPC progression and the possible therapeutic implications. Full article
(This article belongs to the Special Issue Hormone Dependent Cancers: Molecular Mechanisms and Therapeutical Implications)
►▼ Show Figures

Figure 1

17 pages, 1230 KiB  
Review
Role of Gonadotropin-Releasing Hormone (GnRH) in Ovarian Cancer
by Carsten Gründker and Günter Emons
Cells 2021, 10(2), 437; https://doi.org/10.3390/cells10020437 - 18 Feb 2021
Cited by 21 | Viewed by 4801
Abstract
The hypothalamus–pituitary–gonadal (HPG) axis is the endocrine regulation system that controls the woman’s cycle. The gonadotropin-releasing hormone (GnRH) plays the central role. In addition to the gonadotrophic cells of the pituitary, GnRH receptors are expressed in other reproductive organs, such as the ovary [...] Read more.
The hypothalamus–pituitary–gonadal (HPG) axis is the endocrine regulation system that controls the woman’s cycle. The gonadotropin-releasing hormone (GnRH) plays the central role. In addition to the gonadotrophic cells of the pituitary, GnRH receptors are expressed in other reproductive organs, such as the ovary and in tumors originating from the ovary. In ovarian cancer, GnRH is involved in the regulation of proliferation and metastasis. The effects on ovarian tumors can be indirect or direct. GnRH acts indirectly via the HPG axis and directly via GnRH receptors on the surface of ovarian cancer cells. In this systematic review, we will give an overview of the role of GnRH in ovarian cancer development, progression and therapy. Full article
(This article belongs to the Special Issue Hormone Dependent Cancers: Molecular Mechanisms and Therapeutical Implications)
►▼ Show Figures

Figure 1

21 pages, 1521 KiB  
Review
The Role of Gonadotropin-Releasing Hormone (GnRH) in Endometrial Cancer
by Günter Emons and Carsten Gründker
Cells 2021, 10(2), 292; https://doi.org/10.3390/cells10020292 - 1 Feb 2021
Cited by 29 | Viewed by 7483
Abstract
Endometrial cancer (EC) is one of the most common gynecological malignancies. Gonadotropin releasing hormone (GnRH) is a decapeptide first described to be secreted by the hypothalamus to regulate pituitary gonadotropin secretion. In this systematic review, we analyze and summarize the data indicating that [...] Read more.
Endometrial cancer (EC) is one of the most common gynecological malignancies. Gonadotropin releasing hormone (GnRH) is a decapeptide first described to be secreted by the hypothalamus to regulate pituitary gonadotropin secretion. In this systematic review, we analyze and summarize the data indicating that most EC express GnRH and its receptor (GnRH-R) as part of an autocrine system regulating proliferation, the cell cycle, and apoptosis. We analyze the available data on the expression and function of GnRH-II, its putative receptor, and its signal transduction. GnRH-I and GnRH-II agonists, and antagonists as well as cytotoxic GnRH-I analogs, have been shown to inhibit proliferation and to induce apoptosis in human EC cell lines in pre-clinical models. Treatment with conventional doses of GnRH-agonists that suppress pituitary gonadotropin secretion and ovarian estrogen production has become part of fertility preserving therapy of early EC or its pre-cancer (atypical endometrial hyperplasia). Conventional doses of GnRH-agonists had marginal activity in advanced or recurrent EC. Higher doses or more potent analogs including GnRH-II antagonists have not yet been used clinically. The cytotoxic GnRH-analog Zoptarelin Doxorubicin has shown encouraging activity in a phase II trial in patients with advanced or recurrent EC, which expressed GnRH-R. In a phase III trial in patients with EC of unknown GnRH-R expression, the cytotoxic GnRH doxorubicin conjugate was not superior to free doxorubicin. Further well-designed clinical trials exploiting the GnRH-system in EC might be useful. Full article
(This article belongs to the Special Issue Hormone Dependent Cancers: Molecular Mechanisms and Therapeutical Implications)
►▼ Show Figures

Figure 1

23 pages, 1245 KiB  
Review
Hormone Receptor Loss in Breast Cancer: Molecular Mechanisms, Clinical Settings, and Therapeutic Implications
by Emma Zattarin, Rita Leporati, Francesca Ligorio, Riccardo Lobefaro, Andrea Vingiani, Giancarlo Pruneri and Claudio Vernieri
Cells 2020, 9(12), 2644; https://doi.org/10.3390/cells9122644 - 9 Dec 2020
Cited by 30 | Viewed by 5006
Abstract
Hormone receptor-positive breast cancer (HR+ BC) accounts for approximately 75% of new BC diagnoses. Despite the undisputable progresses obtained in the treatment of HR+ BC in recent years, primary or acquired resistance to endocrine therapies still represents a clinically relevant issue, and is [...] Read more.
Hormone receptor-positive breast cancer (HR+ BC) accounts for approximately 75% of new BC diagnoses. Despite the undisputable progresses obtained in the treatment of HR+ BC in recent years, primary or acquired resistance to endocrine therapies still represents a clinically relevant issue, and is largely responsible for disease recurrence after curative surgery, as well as for disease progression in the metastatic setting. Among the mechanisms causing primary or acquired resistance to endocrine therapies is the loss of estrogen/progesterone receptor expression, which could make BC cells independent of estrogen stimulation and, consequently, resistant to estrogen deprivation or the pharmacological inhibition of estrogen receptors. This review aims at discussing the molecular mechanisms and the clinical implications of HR loss as a result of the therapies used in the neoadjuvant setting or for the treatment of advanced disease in HR+ BC patients. Full article
(This article belongs to the Special Issue Hormone Dependent Cancers: Molecular Mechanisms and Therapeutical Implications)
►▼ Show Figures

Figure 1

15 pages, 1617 KiB  
Review
Estrogen Actions in Triple-Negative Breast Cancer
by Oliver Treeck, Susanne Schüler-Toprak and Olaf Ortmann
Cells 2020, 9(11), 2358; https://doi.org/10.3390/cells9112358 - 26 Oct 2020
Cited by 42 | Viewed by 4654
Abstract
Triple-negative breast cancer (TNBC) lacks estrogen receptor (ER) α, but the expression of estrogen receptors ERβ and G protein-coupled estrogen receptor 1 (GPER-1) is able to trigger estrogen-responsivity in TNBC. Estrogen signaling in TNBC can also be activated and modulated by the constitutively [...] Read more.
Triple-negative breast cancer (TNBC) lacks estrogen receptor (ER) α, but the expression of estrogen receptors ERβ and G protein-coupled estrogen receptor 1 (GPER-1) is able to trigger estrogen-responsivity in TNBC. Estrogen signaling in TNBC can also be activated and modulated by the constitutively active estrogen-related receptors (ERRs). In this review article, we discuss the role of ERβ and GPER-1 as mediators of E2 action in TNBC as well as the function of ERRs as activators and modulators of estrogen signaling in this cancer entity. For this purpose, original research articles on estrogen actions in TNBC were considered, which are listed in the PubMed database. Additionally, we performed meta-analyses of publicly accessible integrated gene expression and survival data to elucidate the association of ERβ, GPER-1, and ERR expression levels in TNBC with survival. Finally, options for endocrine therapy strategies for TNBC were discussed. Full article
(This article belongs to the Special Issue Hormone Dependent Cancers: Molecular Mechanisms and Therapeutical Implications)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-9
Back to TopTop