Article
Cell Biology
Yueli Liu, Jiawen Wang, Corrigan Horton, Chuan Yu, Beatrice Knudsen, Joshua Stefanson, Kevin Hu, Ofir Stefanson, Jonathan Green, Charlene Guo, Qing Xie, Zhu A. Wang
Summary: This study reveals that stromal AR inhibits prostate cancer progression by restraining secretory luminal cells, and deletion of stromal AR exacerbates tumor progression and leads to changes in the cellular state of secretory luminal cells.
Article
Multidisciplinary Sciences
Mark D. Long, Vineet K. Dhiman, Hayley C. Affronti, Qiang Hu, Song Liu, Dominic J. Smiraglia
Summary: Understanding the epigenetic control of normal differentiation programs can provide valuable information about the disrupted regulatory states in cancer. By studying the luminal cell differentiation trajectory in prostate cancer cells exposed to androgens, and analyzing DNA methylation dynamics using whole genome bisulfite sequencing, researchers found that aberrant methylation patterns observed in prostate cancer are influenced by the normal dynamics of DNA methylation in the luminal differentiation program.
SCIENTIFIC REPORTS
(2021)
Review
Cell Biology
Qianyao Tang, Bo Cheng, Rongyang Dai, Ronghao Wang
Summary: Prostate cancer (PCa) is the second most lethal cancer for men in western countries, with androgen receptor (AR) playing a central role in its initiation and progression. The interactions between stromal cells and PCa epithelial cells, mediated by AR signaling, impact the growth and invasiveness of PCa cells. Androgen deprivation therapy (ADT) treatment can enhance the reciprocal interaction between stromal and epithelial cells, promoting cell invasion of PCa cells.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Oncology
Konsta Kukkonen, Bryn Autio-Kimura, Hanna Rauhala, Juha Kesseli, Matti Nykter, Leena Latonen, Tapio Visakorpi
Summary: Development of a cell line model mimicking luminal prostate epithelial cells by modifying the immortalized prostate epithelial cell line RWPE-1 to constitutively express the androgen receptor provides a valuable tool for studying the transformation of the prostate epithelium.
ENDOCRINE-RELATED CANCER
(2022)
Article
Biochemistry & Molecular Biology
Waqas Azeem, Jan Roger Olsen, Margrete Reime Hellem, Yaping Hua, Kristo Marvyin, Xisong Ke, Anne Margrete oyan, Karl-Henning Kalland
Summary: This study investigated the role of GATA2 in prostate epithelial cells and found that exogenous GATA2 protein was rapidly degraded and its expression could be rescued by proteasome inhibitors. The inhibition of proteasome also induced the transcription of AR mRNA and luminal marker genes in prostate cells. Different intrinsic mechanisms restricted the expression of GATA2 in these cells. These findings suggest the existence of crucial cofactors for AR mRNA expression and luminal differentiation at the proteolytic level.
Review
Biochemistry & Molecular Biology
Rahul Advani, Sara Luzzi, Emma Scott, Caroline Dalgliesh, Joachim Weischenfeldt, Jennifer Munkley, David J. Elliott
Summary: This article discusses the expression of splicing regulators ESRP1 and ESRP2 in aggressively proliferating primary prostate tumors as markers of disease progression. It suggests that ESRP1 and ESRP2 act as lineage survival oncogenes in prostate cancer and highlights the need to identify the gene expression targets controlled by these regulators to develop targeted therapies.
Article
Oncology
Sophie Bartsch, Kimia Mirzakhani, Laura Neubert, Alexander Stenzel, Marzieh Ehsani, Mohsen Esmaeili, Thanakorn Pungsrinont, Merve Kacal, Seyed Mohammad Mahdi Rasa, Julia Kallenbach, Divya Damodaran, Federico Ribaudo, Marc-Oliver Grimm, Francesco Neri, Aria Baniahmad
Summary: The expression of human telomerase reverse transcriptase subunit (hTERT) is hormonally controlled, with androgen treatment suppressing hTERT expression in prostate cancer cells. This inhibition and activation of hTERT by androgens is mediated by androgen receptor (AR) co-repressors ING1 and ING2. This reveals a dual role of AR in controlling hTERT expression during prostate cancer tumorigenesis.
Review
Medicine, Research & Experimental
Joanna Dulinska-Litewka, Dominik Felkle, Kacper Dykas, Zuzanna Handziuk, Marta Krzysztofik, Bartosz Gasiorkiewicz
Summary: The role of cyclins in hormone-dependent neoplasms, especially breast cancer, is crucial. However, cyclins in prostate cancer are less studied, particularly the role of other cyclins that requires further investigation. Recent studies have shown that cyclins not only regulate the cell cycle but also interact with other signaling pathways. The androgen signaling axis plays a significant role in prostate cancer progression and interferes with cyclin pathways.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Oncology
Miki Naito, Kenichiro Ikeda, Shunya Aoyama, Mayu Kanamoto, Yasuyuki Akasaka, Yuri Kido, Mikako Nakanishi, Machi Kanna, Takeshi Yamamotoya, Akio Matsubara, Nobuyuki Hinata, Tomoichiro Asano, Yusuke Nakatsu
Summary: Par14, an isoform of Pin1 homologous to prolyl isomerases, is shown to be overexpressed in prostate cancer (PCa) and plays a critical role in PCa progression. It enhances the growth of androgen-sensitive LNCap cells and regulates the expression of androgen response genes through its association with AR and modulation of p53 localization. These findings suggest Par14 as a potential therapeutic target for PCa.
Article
Cell Biology
Katie Joanna Miller, Mohammad Asim
Summary: The androgen receptor (AR) signalling pathway plays a key role in prostate cancer. Upstream kinases promote AR signalling, while other kinases are regulated by AR. These kinases represent potential therapeutic targets for PCa.
Article
Biology
Russell J. Ledet, Sophie E. Ruff, Yu Wang, Shruti Nayak, Jeffrey A. Schneider, Beatrix Ueberheide, Susan K. Logan, Michael J. Garabedian
Summary: Through a chemical genetics screen and phospho-proteomics, Ledet and Ruff et al identify substrates of the oncogenic kinase PIM1 in prostate cancer cells. They find that NDRG1 protein is destabilized by PIM1-mediated phosphorylation to reduce its metastasis suppressor function. These findings shed light on the role of PIM1 in prostate cancer.
COMMUNICATIONS BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Jae Duck Choi, Tae Jin Kim, Byong Chang Jeong, Hwang Gyun Jeon, Seong Soo Jeon, Min Yong Kang, Seon Yong Yeom, Seong Il Seo
Summary: Abnormal expression of ISL1 has been closely associated with cancer development and progression, with particular focus on its role in the androgen receptor-dependent prostate cancer cell growth, EMT, and enzalutamide resistance. ISL1 knockdown was found to inhibit AR activity, cell growth, and EMT in enzalutamide-resistant cells, suggesting its potential as a therapeutic target for CRPC. The study highlights the importance of downregulating ISL1 expression to overcome enzalutamide resistance and improve survival in CRPC patients.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Lenny K. Hong, Shrinidhi Kadkol, Maria Sverdlov, Irida Kastrati, Mostafa Elhodaky, Ryan Deaton, Karen S. Sfanos, Heidi Wang, Li Liu, Alan M. Diamond
Summary: SELENOF is a selenoprotein involved in prostate cancer, with polymorphisms in the 3'-UTR region affecting the risk of prostate cancer mortality in African American men. Low levels of SELENOF in prostate cancer tissues may contribute to tumor progression and metastasis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Demitria M. Vasilatis, Christopher A. Lucchesi, Paramita M. Ghosh
Summary: Dogs naturally develop prostate cancer similar to aggressive forms found in humans. Prostate cancer samples in dogs often lack androgen receptor (AR), which can enhance our understanding of AR-indifferent prostate cancer in humans. This review highlights the molecular similarities between dog and human prostate cancer variants, suggesting the potential use of dogs as pre-clinical animal models for developing new therapies and diagnostics that can benefit both species.
Article
Oncology
Jiaqian Liang, Liyang Wang, Larysa Poluben, Mannan Nouri, Seiji Arai, Lisha Xie, Olga S. Voznesensky, Laura Cato, Xin Yuan, Joshua W. Russo, Henry W. Long, Myles Brown, Shaoyong Chen, Steven P. Balk
Summary: In castration-resistant prostate cancer (CRPC), the splice variant ARv7 can function independently of the full length ARfl, with both contributing independently to overall AR activity.
Article
Oncology
Dong Chen, Fu-Ju Chou, Yuhchyau Chen, Hao Tian, Yaqin Wang, Bosen You, Yuanjie Niu, Chi-Ping Huang, Shuyuan Yeh, Nianzeng Xing, Chawnshang Chang
Article
Biochemistry & Molecular Biology
Guodong Liu, Xiwu Ouyang, Yin Sun, Yao Xiao, Bosen You, Yuan Gao, Shuyuan Yeh, Yixiong Li, Chawnshang Chang
CELL DEATH AND DIFFERENTIATION
(2020)
Article
Biochemistry & Molecular Biology
Qingbo Huang, Yin Sun, Wei Zhai, Xin Ma, Donglai Shen, Songliang Du, Bosen You, Yuanjie Niu, Chi-Ping Huang, Xu Zhang, Chawnshang Chang
Article
Oncology
Hao Tian, Fu-ju Chou, Jing Tian, Yong Zhang, Bosen You, Chi-Ping Huang, Shuyuan Yeh, Yuanjie Niu, Chawnshang Chang
Summary: ASC-J9 (R) can suppress prostate cancer progression via an androgen receptor-independent mechanism by altering ATF3 expression, leading to decreased PTK2 expression. Clinical and preclinical studies support the role of ATF3/PTK2 signaling in PCa progression.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Article
Cell Biology
Zhendong Xiang, Yin Sun, Bosen You, Meng Zhang, Chiping Huang, Junfeng Yu, Xiangyun You, Denglong Wu, Chawnshang Chang
Summary: The study found that Enzalutamide-resistant prostate cancer cells can be suppressed by high doses of the androgen DHT. Targeting the BCL-XL protein can enhance the inhibitory effect of high-dose DHT on cell growth, promoting cell death.
CELL DEATH & DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Bosen You, Yin Sun, Jie Luo, Keliang Wang, Qing Liu, Ruizhe Fang, Bingmei Liu, Fuju Chou, Ronghao Wang, Jialin Meng, Chi-Ping Huang, Shuyuan Yeh, Chawnshang Chang, Wanhai Xu
Summary: The study suggests that androgen receptor (AR) promotes vasculogenic mimicry (VM) formation in ccRCC cells by regulating lncRNA-TANAR/TWIST1 signals, potentially impacting metastasis. This discovery provides a clue for the development of a novel anti-angiogenesis therapy to better suppress ccRCC progression.
Article
Oncology
Dongkui Gong, Yin Sun, Changcheng Guo, Tzong-jen Sheu, Wei Zhai, Junhua Zheng, Chawnshang Chang
Summary: The study revealed gender differences in RBM, with higher AR expression potentially linked to fewer RBMs by suppressing osteolytic formation. Mechanism dissection showed that AR can decrease circEXOC7 expression by enhancing transcription of DHX9, leading to suppression of CSF1 expression. Results from clinical epidemiological surveys found positive correlation between AR and miR-149-3p, and negative correlation between AR and CSF1 in AR-positive ccRCC tissues.
CLINICAL AND TRANSLATIONAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Gang Deng, Ronghao Wang, Yin Sun, Chi-Ping Huang, Shuyuan Yeh, Bosen You, Changyong Feng, Gonghui Li, Shenglin Ma, Chawnshang Chang
Summary: Targeting androgens/androgen receptor signals can affect the invasion capability of prostate cancer and bladder cancer cells, with prostate cancer cell invasion increasing while bladder cancer cell invasion decreasing. This difference may be due to the distinct alterations in selective circular RNAs resulting from differential endogenous AR transcription, along with differential histone H3K4 methylation patterns and binding of AR to different androgen-response elements.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Cell Biology
Meng Zhang, Yin Sun, Chi-Ping Huang, Jie Luo, Li Zhang, Jialin Meng, Chaozhao Liang, Chawnshang Chang
Summary: The study identified that lnc-OPHN1-5 plays a role in increasing prostate cancer sensitivity to Enzalutamide by regulating AR protein expression. The mechanism involves lnc-OPHN1-5 interacting with AR-mRNA to influence ribosome association and translation by modulating hnRNPA1.
CELL DEATH & DISEASE
(2021)
Article
Cell Biology
Kuo-Chung Lan, Kuo-Ting Wei, Pei-Wen Lin, Ching-Chen Lin, Pei-Ling Won, Ya-Fen Liu, Yun-Ju Chen, Bi-Hua Cheng, Tien-Min G. Chu, Jia-Feng Chen, Ko-En Huang, Chawnshang Chang, Hong-Yo Kang
Summary: The study found that androgen receptor (AR) is highly expressed in periosteum cells during bone fracture repair and is co-localized with a mesenchymal progenitor cell marker, Prrx1. Mice lacking AR in periosteum showed reduced callus size and new bone volume. Targeting the androgen/AR axis in periosteum may provide a novel therapy approach to improve fracture healing.
CELL DEATH & DISEASE
(2022)
Article
Oncology
Jie Ding, Xin-Gang Cui, Hao-Jie Chen, Yin Sun, Wei-Wei Yu, Jie Luo, Guang-Qian Xiao, Chawnshang Chang, Jun Qi, Shuyuan Yeh
Summary: Vasculogenic mimicry (VM), an alternative channel for tumor nutrient supply, is associated with poor prognosis in renal cell carcinoma (RCC). Sunitinib, a tyrosine kinase inhibitor (TKI), has been reported to induce VM formation by up-regulating estrogen receptor beta (ERβ) expression. This study showed that treatment with sunitinib and another TKI, axitinib, also induced ERβ expression in RCC cell lines. Clinical RCC patients with higher ERβ expression were more likely to have VM. Mechanistically, TKI-induced ERβ up-regulated the circular RNA DGKD, which enhanced VM formation by increasing VE-cadherin expression. Targeting circDGKD intercepted sunitinib-induced RCC VM formation and improved survival in an animal model.
Article
Cell Biology
Lei Chen, Yin Sun, Min Tang, Denglong Wu, Zhendong Xiang, Chi-Ping Huang, Bosen You, Dongdong Xie, Qinglin Ye, Dexin Yu, Chawnshang Chang
Summary: This study found that high-dose androgens can suppress the growth of Enzalutamide-resistant (EnzR) castration-resistant prostate cancer (CRPC) cells. The mechanism involves the transcriptional regulation of the circRNA-BCL2 host gene BCL2, which in turn affects the expression of miRNA-198 and modulates the expression of AMBRA1. This leads to the induction of autophagic cell death and the suppression of EnzR CRPC cell growth.
CELL DEATH DISCOVERY
(2022)
Article
Cell Biology
Yang Yang, Jindong Sheng, Shuai Hu, Yun Cui, Jing Xiao, Wei Yu, Jing Peng, Wenke Han, Qun He, Yu Fan, Yuanjie Niu, Jun Lin, Ye Tian, Chawnshang Chang, Shuyuan Yeh, Jie Jin
Summary: This study identified the histopathological characteristics and molecular mechanisms underlying accelerated progression of benign prostatic hyperplasia (BPH). Increased stromal components and prostatic fibrosis, accompanied by higher myofibroblast accumulation and collagen deposition, were found to be the main features of accelerated progressive BPH tissues. Mechanism dissection revealed that higher expression of CYP19 and G protein-coupled estrogen receptor (GPER) with higher estrogen biosynthesis contribute to the progression of BPH. Targeting the CYP19/estrogen/GPER/G alpha i signaling axis may provide new personalized therapeutics for better suppressing the progression of BPH.
CELL DEATH & DISEASE
(2022)
Article
Medicine, Research & Experimental
Juan Pablo Arroyo, Andrew S. Terker, Yvonne Zuchowski, Jason A. Watts, Fabian Bock, Cameron Meyer, Wentian Luo, Meghan E. Kapp, Edward R. Gould, Adam X. Miranda, Joshua Carty, Ming Jiang, Roberto M. Vanacore, Elizabeth Hammock, Matthew H. Wilson, Roy Zent, Mingzhi Zhang, Gautam Bhave, Raymond C. Harris
Summary: Research has found that vasopressin can be produced in the kidneys, specifically in the tubular epithelial cells of mouse and human kidneys. This kidney-derived vasopressin is biologically active and regulated by hypertonic conditions and water restriction.
Article
Medicine, Research & Experimental
Yu Pan, Shirong Cao, Jiaqi Tang, Juan P. Arroyo, Andrew S. Terker, Yinqiu Wang, Aolei Niu, Xiaofeng Fan, Suwan Wang, Yahua Zhang, Ming Jiang, David H. Wasserman, Ming-Zhi Zhang, Raymond C. Harris
Summary: Obesity-related complications are causing increasing morbidity and mortality worldwide, mainly due to inflammation and dysregulated metabolism in adipose tissue leading to insulin resistance and metabolic syndrome. Studies have shown that the ATM COX-2/PGE2/EP4 axis in adipose tissue plays a critical role in inhibiting adipose tissue dysfunction during obesity.
JOURNAL OF CLINICAL INVESTIGATION
(2022)