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Molecular Signaling in Prostate Development and Prostate Cancer

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

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 10363

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Special Issue Editor

Dr. Wen-Yang Hu

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Guest Editor

Department of Urology, University of Illinois at Chicago, 820 South Wood Street, M/C 955, Chicago, IL 60612, USA
Interests: gene; stem cells; progenitor cells; xenograft model; cancer; basic molecular biology techniques

Special Issue Information

Dear Colleagues,

Developmental biology has immensely contributed to cancer research. Accumulating evidence indicates that cancer is a problem originating during developmental stages. Cancers resemble development in many aspects: cancer cells are heterogeneous and undifferentiated like embryonic stem cells; cancer cells are highly invasive with increased mobility resembling migratory behavior during development; genome-wide transcriptome profiling has revealed common gene signatures in several cancers and in the early developmental stages of their tissue of origin; and many developmental genes, including transcription factors, originally identified in embryonic tissues as playing important roles in cell growth and differentiation are frequently silenced in adults but become mutated and are reactivated in tumor tissues.

Genetic and environmental factors may, together, disrupt critical epigenetic processes during development, affecting gene-related signaling pathways, biological processes, and cellular functions. Although there are distinct time periods of heightened susceptibility to cancer-causing substances that exist throughout the life course, compelling studies have shown that the influence of environmental chemicals on cancer risk is greater during prenatal development and puberty. Thus, developmental stages are considered specific windows of susceptibility for many cancers including prostate cancer. Early exposures to endocrine disruptors permanently modify the epigenetics of developmental imprinting genes that subsequently reprogram and transform prostate stem cells to initiate prostatic carcinogenesis.

Although it is not clear whether this is a universal feature of malignancy, the similarities of developmental biology and cancer biology along with their continuing research will provide us with windows of opportunity for successful prevention programs and therapeutic strategies for cancers. The current open-access Special Issue entitled “Molecular Signaling in Prostate Development and Prostate Cancer” aims to compile scientific studies with cutting edge research to gain further insights into developmental biology and cancer biology in the prostate. Original research articles and comprehensive reviews covering prostate developmental biology and/or prostate cancer biology are welcome.

Dr. Wen-Yang Hu
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. 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

prostate
development
cancer
biology
molecular signaling
environmental factors
epigenetic
stem cell

Published Papers (4 papers)

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Research

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16 pages, 3824 KiB

Open AccessArticle

Morphometric Analysis of Rat Prostate Development: Roles of MEK/ERK and Rho Signaling Pathways in Prostatic Morphogenesis

by Wen-Yang Hu, Parivash Afradiasbagharani, Ranli Lu, Lifeng Liu, Lynn A. Birch and Gail S. Prins

Biomolecules 2021, 11(12), 1829; https://doi.org/10.3390/biom11121829 - 4 Dec 2021

Cited by 1 | Viewed by 2103

Abstract

The molecular mechanisms underlying prostate development can provide clues for prostate cancer research. It has been demonstrated that MEK/ERK signaling downstream of androgen-targeted FGF10 signaling directly induces prostatic branching during development, while Rho/Rho-kinase can regulate prostate cell proliferation. MEK/ERK and Rho/Rho kinase regulate myosin light chain kinase (MLCK), and MLCK regulates myosin light chain phosphorylation (MLC-P), which is critical for cell fate, including cell proliferation, differentiation, and apoptosis. However, the roles and crosstalk of the MEK/ERK and Rho/Rho kinase signaling pathways in prostatic morphogenesis have not been examined. In the present study, we used numerical and image analysis to characterize lobe-specific rat prostatic branching during postnatal organ culture and investigated the roles of FGF10-MEK/ERK and Rho/Rho kinase signaling pathways in prostatic morphogenesis. Prostates exhibited distinctive lobe-specific growth and branching patterns in the ventral (VP) and lateral (LP) lobes, while exogenous FGF10 treatment shifted LP branching towards a VP branching pattern. Treatment with inhibitors of MEK1/2, Rho, Rho kinase, or MLCK significantly inhibited VP growth and blocked branching morphogenesis, further supporting critical roles for MEK/ERK and Rho/Rho kinase signaling pathways in prostatic growth and branching during development. We propose that MLCK-regulated MLC-P may be a central downstream target of both signaling pathways in regulating prostate morphogenesis. Full article

(This article belongs to the Special Issue Molecular Signaling in Prostate Development and Prostate Cancer)

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11 pages, 2220 KiB

Open AccessCommunication

NK Cells Can Preferentially Target Prostate Cancer Stem-like Cells via the TRAIL/DR5 Signaling Pathway

by Taiga Seki, Yui Shimizu, Kyota Ishii, Yuzuki Takahama, Kazunori Kato and Tomohiro Yano

Biomolecules 2021, 11(11), 1702; https://doi.org/10.3390/biom11111702 - 16 Nov 2021

Cited by 8 | Viewed by 1912

Abstract

Background: The occurrence of androgen-dependent prostate cancer mainly depends on prostate cancer stem cells. To reduce the risk of androgen-dependent prostate cancer, the direct elimination of prostate cancer stem cells is important, but an elimination strategy has not yet been established. A previous study showed that natural killer (NK) cells can preferentially target cancer stem cells in several solid tumors except prostate cancer. In this context, this study was undertaken to investigate if NK cells can selectively attack androgen-dependent prostate cancer stem cells. Methods: Prostate cancer stem-like cells were separated from an androgen-dependent prostate cancer cell line (LNCaP) using a three-dimensional culture system. LNCaP stem-like cells or LNCaP cells were co-cultured with human NK cells (KHYG-1) for 24–72 h, and cell viability was determined using the WST-8 method. The expression of each protein in the cell membrane was evaluated through FACS analysis, and mRNA levels were determined using real-time PCR. Results: KHYG-1 cells had more potent cytotoxicity against LNCaP stem-like cells than LNCaP cells, and the potency of the cytotoxicity was strongly related to the TRAIL/DR5 cell death pathway. Conclusion: NK cells can preferentially target prostate cancer stem-like cells via the TRAIL/DR5 pathway. Full article

(This article belongs to the Special Issue Molecular Signaling in Prostate Development and Prostate Cancer)

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16 pages, 4440 KiB

Open AccessArticle

PAQR6 Upregulation Is Associated with AR Signaling and Unfavorite Prognosis in Prostate Cancers

by Min Yang, Jean Chong Li, Chang Tao, Sa Wu, Bin Liu, Qiang Shu, Benyi Li and Runzhi Zhu

Biomolecules 2021, 11(9), 1383; https://doi.org/10.3390/biom11091383 - 18 Sep 2021

Cited by 12 | Viewed by 2648

Abstract

Progesterone-induced rapid non-genomic signaling events have been confirmed through several membrane progesterone receptors (mPR). Some mPRs were reported to correlate with cancer progression and patient prognosis. In this study, we conducted a comprehensive analysis of all progesterone receptor (PGR)-related genes in prostate cancer tissues and examined the correlations of their expression levels with disease progression and patient survival outcomes. We utilized multiple RNA-seq and cDNA microarray datasets to analyze gene expression profiles and performed logistics aggression and Kaplan-Meier survival analysis after stratifying patients based on tumor stages and Gleason scores. We also used NCBI GEO datasets to examine gene expression patterns in individual cell types of the prostate gland and to determine the androgen-induced alteration of gene expression. Spearman coefficient analysis was conducted to access the correlation of target gene expression with treatment responses and disease progression status. The classic PGR was mainly expressed in stromal cells and progestin and adipoQ receptor (PAQR) genes were the predominant genes in prostate epithelial cells. Progesterone receptor membrane component-1 (PGRMC1) was significantly higher than PGRMC2 in all prostate cell types. In prostate cancer tissues, PAQR6 expression was significantly upregulated, while all other genes were largely downregulated compared to normal prostate tissues. Although both PAQR6 upregulation and PAQR5 downregulation were significantly correlated with tumor pathological stages, only PAQR6 upregulation was associated with Gleason score, free-prostate-specific antigen (fPSA)/total-PSA (tPSA) ratio, and patient overall survival outcomes. In addition, PAQR6 upregulation and PGR/PGRMC1 downregulation were significantly associated with a quick relapse. Conversely, in neuroendocrinal prostate cancer (NEPC) tissues, PAQR6 expression was significantly lower, but PAQR7/8 expression was higher than castration-resistant prostate cancer (CRPC) tissues. PAQR8 expression was positively correlated with androgen receptor (AR) score and AR-V7 expression levels but inversely correlated with NEPC score in metastatic CRPC tumors. This study provides detailed expression profiles of membrane progesterone receptor genes in primary cancer, CRPC, and NEPC tissues. PAQR6 upregulation in primary cancer tissues is a novel prognostic biomarker for disease progression, overall, and progression-free survival in prostate cancers. PAQR8 expression in CRPC tissues is a biomarker for AR activation. Full article

(This article belongs to the Special Issue Molecular Signaling in Prostate Development and Prostate Cancer)

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Review

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14 pages, 2276 KiB

Open AccessReview

Clinical Significance of Hepsin and Underlying Signaling Pathways in Prostate Cancer

by Lucy Lu, Adam Cole, Dan Huang, Qiang Wang, Zhongming Guo, Wancai Yang and Jim Lu

Biomolecules 2022, 12(2), 203; https://doi.org/10.3390/biom12020203 - 25 Jan 2022

Cited by 7 | Viewed by 2769

Abstract

The hepsin gene encodes a type II transmembrane serine protease. Previous studies have shown the overexpression of hepsin in prostate cancer, and the dysregulation of hepsin promotes cancer cell proliferation, migration, and metastasis in vitro and in vivo. The review incorporated with our work showed that hepsin expression levels were specifically increased in prostate cancer, and higher expression in metastatic tumors than in primary tumors was also observed. Moreover, increased expression was associated with poor outcomes for patients with prostate cancer. Using in silico protein–protein interaction prediction, mechanistic analysis showed that hepsin interacted with eight other oncogenic proteins, whose expression was significantly correlated with hepsin expression in prostate cancer. The oncogenic functions of hepsin are mainly linked to proteolytic activities that disrupt epithelial integrity and regulatorily interact with other genes to influence cell-proliferation, EMT/metastasis, inflammatory, and tyrosine-kinase-signaling pathways. Moreover, genomic amplifications of hepsin, not deletions or other alterations, were significantly associated with prostate cancer metastasis. Targeting hepsin using a specific inhibitor or antibodies significantly attenuates its oncogenic behaviors. Therefore, hepsin could be a novel biomarker and therapeutic target for prostate cancer. Full article

(This article belongs to the Special Issue Molecular Signaling in Prostate Development and Prostate Cancer)

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