Article
Endocrinology & Metabolism
Hamsa Thayele Purayil, Yehia Daaka
Summary: This study found that increased expression of beta arrestin1 (beta Arr1) is positively correlated with increased glucocorticoid receptor (GR) expression and function in castration-resistant prostate cancer (CRPC) xenografts and human PC patients. Beta Arr1 forms a complex with GR in the nucleus, and targeting the beta Arr1-GR axis may provide a new opportunity for managing CRPC.
Article
Oncology
Rafael S. Martinez, Mark J. Salji, Linda Rushworth, Chara Ntala, Giovanny Rodriguez Blanco, Ann Hedley, William Clark, Paul Peixoto, Eric Hervouet, Elodie Renaude, Sonia H. Y. Kung, Laura C. A. Galbraith, Colin Nixon, Sergio Lilla, Gillian M. Mackay, Ladan Fazli, Luke Gaughan, David Sumpton, Martin E. Gleave, Sara Zanivan, Arnaud Blomme, Hing Y. Leung
Summary: This study identified SLFN5 as a novel regulator of the LAT1 amino acid transporter in castration-resistant prostate cancer (CRPC), contributing to mTORC1 activity. High expression of SLFN5 in CRPC tumors was correlated with poor patient outcome, indicating its clinical relevance as a potential target for CRPC treatment.
Article
Biochemistry & Molecular Biology
Hamsa Thayele Purayil, Yushan Zhang, Joseph B. Black, Raad Gharaibeh, Yehia Daaka
Summary: This study identified beta Arrestin 1 (beta Arr1) as a regulator of androgen receptor (AR) function in castration-resistant prostate cancer (CRPC). Beta Arr1 forms a complex with AR and beta Catenin in the nucleus, enhancing AR transcriptional function in CRPC. Depletion of beta Arr1 attenuates PC cell and tumor growth, while restoring nuclear beta Arr1 expression restores these processes. Targeting beta Arr1-regulated AR transcriptional function may lead to the development of new drugs for lethal CRPC.
Article
Oncology
Emuejevoke Olokpa, Sammed N. Mandape, Siddharth Pratap, La Monica Stewart
Summary: The study used RNA sequencing to identify the signaling pathways regulated by metformin in androgen-receptor positive, castration-resistant prostate cancer cells. Metformin was found to alter the expression of genes involved in metabolic pathways, the spliceosome, RNA transport, and protein processing within the endoplasmic reticulum, as well as in ErbB, insulin, mTOR, TGF-beta, MAPK, and Wnt signaling pathways. Some of the metformin-regulated genes are known to be direct transcriptional targets of p53 or AR, and metformin-induced reductions in AR mRNA and protein levels contributed to these alterations in gene expression.
Review
Urology & Nephrology
Soum D. Lokeshwar, Zachary Klaassen, Fred Saad
Summary: Metastatic prostate cancer is associated with high morbidity and mortality rates. Treatment of non-metastatic prostate cancer often involves androgen deprivation therapy (ADT), but many patients eventually develop castration-resistant prostate cancer (CRPC). A new stage called non-metastatic CRPC (nmCRPC) has gained attention, with three novel nonsteroidal antiandrogens (enzalutamide, apalutamide, darolutamide) showing promising results in clinical trials.
NATURE REVIEWS UROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Arielle Shkedi, Isabelle R. Taylor, Frank Echtenkamp, Poornima Ramkumar, Mohamed Alshalalfa, Genesis M. Rivera-Marquez, Michael A. Moses, Hao Shao, Robert Jeffrey Karnes, Len Neckers, Felix Feng, Martin Kampmann, Jason E. Gestwicki
Summary: Castration-resistant prostate cancer (CRPC) is associated with increased reliance on heat shock protein 70 (HSP70) and mitochondrial chaperone protein, HSP60, is selectively required in CRPC cell lines. Knockdown of HSP60 results in loss of mitochondrial spare respiratory capacity and poor survival in prostate cancer patients.
CELL CHEMICAL BIOLOGY
(2022)
Article
Oncology
Ke Gao, Xiaoshun Li, Jianxin Ni, Bin Wu, Jiaheng Guo, Rui Zhang, Guojun Wu
Summary: This article introduces the roles of dysregulation of different subclasses of non-coding RNAs (ncRNAs) in the development of castration-resistant prostate cancer (CRPC) progression and Enzalutamide (Enz) resistance. The mechanisms of Enz resistance, including AR-splice variant-7 (AR-V7), mutations, circRNAs, and lncRNAs that act as miRNA sponges, are discussed. The contributions of epithelial-mesenchymal transition and glucose metabolism to Enz resistance are also highlighted. The article summarizes the different mechanisms of miRNAs, lncRNAs, and circRNAs in the progression of CRPC and Enz resistance, and discusses future therapeutic strategies against Enz resistance.
Article
Biochemistry & Molecular Biology
Sarina Cameron, Genevieve Deblois, James R. Hawley, Aditi Qamra, Stanley Zhou, Seyed Ali Madani Tonekaboni, Alexander Murison, Romy Van Vliet, Juan Liu, Jason W. Locasale, Mathieu Lupien
Summary: Predicting and treating recurrence in intermediate-risk prostate cancer patients is challenging. This study found that chronic hypoxia leads to an androgen-independent state in prostate cancer cells, promoting cancer progression. These findings may provide additional strategies for treating hypoxic prostate cancer.
Article
Oncology
Frantzeska Giginis, Joshua Wang, Aaron Chavez, Manuela Martins-Green
Summary: Prostate Cancer (PCa) is the second most prevalent cancer in the world. Currently, most treatments for PCa involve Androgen Deprivation Therapy (ADT) which is not effective for metastatic Castration-Resistant Prostate Cancer (mCRPC). Decreasing the enzyme catalase, which reduces oxidative stress levels, has the potential to provide another target for Prostate Cancer therapy.
AMERICAN JOURNAL OF CANCER RESEARCH
(2023)
Article
Multidisciplinary Sciences
Fanying Tang, Duo Xu, Shangqian Wang, Chen Khuan Wong, Alexander Martinez-Fundichely, Cindy J. Lee, Sandra Cohen, Jane Park, Corinne E. Hill, Kenneth Eng, Rohan Bareja, Teng Han, Eric Minwei Liu, Ann Palladino, Wei Di, Dong Gao, Wassim Abida, Shaham Beg, Loredana Puca, Maximiliano Meneses, Elisa de Stanchina, Michael F. Berger, Anuradha Gopalan, Lukas E. Dow, Juan Miguel Mosquera, Himisha Beltran, Cora N. Sternberg, Ping Chi, Howard Scher, Andrea Sboner, Yu Chen, Ekta Khurana
Summary: This study classified CRPC into different subtypes using ATAC-seq, RNA-seq, and DNA sequencing. The identified subtypes include AR-dependent, neuroendocrine, Wnt-dependent, and stem cell-like subtypes driven by AP-1 transcription factors. Transcriptomic signatures were used for patient classification, and SCL was found to be the second most common subtype of CRPC.
Review
Biochemistry & Molecular Biology
Yasemin Sanli, Duygu Has Simsek, Oner Sanli, Rathan M. Subramaniam, Ayse Tuba Kendi
Summary: Lu-177-PSMA therapy shows promising clinical efficacy in patients with mCRPC, with predictors of efficacy being significant. Ongoing clinical trials, including a phase III multicenter FDA registration trial, are currently being conducted in the United States.
Article
Multidisciplinary Sciences
Peter Arnold, Maria Cristina Penaloza-Ramos, Lola Adedokun, Sarah Rees, Mohamed Lockhat, Lisa Spary, Alan Watkins, Vincent Gnanapragasam, Simon J. Crabb
Summary: This study used linked datasets to explore the characteristics and outcomes of prostate cancer patients with non-metastatic castration-resistant PC. Shorter PSA doubling time was associated with quicker progression to metastases or death, while age did not show a significant association with time to metastases or death.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Sanjeev Kumar Srivastava, Mohammad Aslam Khan, Shashi Anand, Haseeb Zubair, Sachin Kumar Deshmukh, Girijesh Kumar Patel, Seema Singh, Joel Andrews, Bin Wang, James Elliot Carter, Ajay Pratap Singh
Summary: The study revealed that MYB and AR interact in prostate cancer cells, and overexpression of MYB can lead to resistance to castration and rapid growth post-castration, resulting in shorter survival of mice.
BRITISH JOURNAL OF CANCER
(2022)
Article
Oncology
Yu-Ching Wen, Chien-Liang Liu, Hsiu-Lien Yeh, Wei-Hao Chen, Kuo-Ching Jiang, Van Thi Ngoc Tram, Michael Hsiao, Jiaoti Huang, Wei-Yu Chen, Yen-Nien Liu
Summary: Our study reveals that LIF/ZBTB46 signaling activation upregulates PCK1-driven glucose metabolism and neuroendocrine differentiation in CRPC. Targeting PCK1 may reduce the neuroendocrine phenotype and inhibit the growth of prostate cancer cells in vitro and in vivo, offering potential improvements in prostate cancer treatment after ADT using PCK1 inhibitors.
BRITISH JOURNAL OF CANCER
(2022)
Article
Oncology
Cedric Pobel, Edouard Auclin, Diego Teyssonneau, Brigitte Laguerre, Mathilde Cancel, Elouen Boughalem, Johanna Noel, Pierre Emmanuel Brachet, Denis Maillet, Philippe Barthelemy, Carole Helissey, Constance Thibault, Stephane Oudard
Summary: Cabazitaxel multiple rechallenges can be a treatment option in heavily pretreated patients with metastatic castration-resistant prostate cancer, with efficacy and manageable toxicity for those who had a good initial response to cabazitaxel.
Article
Biochemistry & Molecular Biology
Hussein Al-Akhrass, James R. W. Conway, Annemarie Svane Aavild Poulsen, Ilkka Paatero, Jasmin Kaivola, Artur Padzik, Olav M. Andersen, Johanna Ivaska
Summary: Resistance to HER2-targeted therapies in breast cancer is often associated with HER3 signaling, and the interaction between SorLA and HER3 has been found to play a key role in regulating the stability of the HER2-HER3 dimer. Loss of SorLA compromises heregulin-induced cell proliferation and sensitizes metastatic anti-HER2 therapy-resistant cells to neratinib, indicating a potential therapeutic target for overcoming resistance mechanisms.
Article
Developmental Biology
Minkyoung Lee, Charles Betz, Jianmin Yin, Ilkka Paatero, Niels Schellinx, Adam N. Carte, Christopher W. Wilson, Weilan Ye, Markus Affolter, Heinz-Georg Belting
Summary: Rasip1 plays essential roles during blood vessel formation by regulating various cellular behaviors such as cell pairing, tricellular junction stability, and apical membrane organization. Loss of Rasip1 function results in defects in sprouting angiogenesis, anastomosis, and lumen formation, highlighting the importance of Rasip1 in maintaining proper multicellular organization and junction formation during vascular development.
Article
Oncology
Lan Yu, Mervi Toriseva, Syeda Afshan, Mario Cangiano, Vidal Fey, Andrew Erickson, Heikki Seikkula, Kalle Alanen, Pekka Taimen, Otto Ettala, Martti Nurmi, Peter J. Bostrom, Markku Kallajoki, Johanna Tuomela, Tuomas Mirtti, Ines J. Beumer, Matthias Nees, Pirkko Harkonen
Summary: This study found that FGFRL1 is significantly upregulated in prostate cancer. Different cellular localizations of FGFRL1 have different effects on clinical indicators. Knockdown of FGFRL1 suppresses xenograft tumor growth, while overexpression attenuates signal transduction. These results suggest that FGFRL1 is involved in prostate cancer progression, and nuclear FGFRL1 could serve as a prognostic marker.
Article
Multidisciplinary Sciences
Riikka Huhtaniemi, Petra Sipila, Arttu Junnila, Riikka Oksala, Matias Knuuttila, Arfa Mehmood, Eija Aho, Teemu D. Laajala, Tero Aittokallio, Asta Laiho, Laura Elo, Claes Ohlsson, Malin Hagberg Thulin, Pekka Kallio, Sari Makela, Mika V. J. Mustonen, Matti Poutanen
Summary: The resistance to antiandrogen treatment is a major issue in the treatment of castration-resistant prostate cancer (CRPC). The intratumor DHT concentration and expression of several androgen-dependent genes can serve as indicators of enzalutamide treatment resistance and the need for further androgen blockade.
Article
Medicine, Research & Experimental
Roope Huttunen, Annele Sainio, Anja Hjelt, Anna-Mari Haapanen-Saaristo, Jorma Maatta, Petri Rummukainen, Ilkka Paatero, Hannu Jarvelainen
Summary: The SGLT2 inhibitor canagliflozin increases the risk for lower limb amputations in type 2 diabetics, while empagliflozin and dapagliflozin do not have the same effect. The study using zebrafish and human umbilical vein endothelial cells (HUVECs) found that different SGLT2 inhibitors have varying effects on angiogenesis and cell viability, indicating that the risk for peripheral amputations may differ among SGLT2 inhibitors.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Oncology
Anna Aakula, Aleksi Isomursu, Christian Rupp, Andrew Erickson, Nikhil Gupta, Otto Kauko, Pragya Shah, Artur Padzik, Yuba Raj Pokharel, Amanpreet Kaur, Song-Ping Li, Lloyd Trotman, Pekka Taimen, Antti Rannikko, Jan Lammerding, Ilkka Paatero, Tuomas Mirtti, Johanna Ivaska, Jukka Westermarck
Summary: This study found that prostate cancer tumors with concomitant inhibition of PP2A and PTEN are particularly aggressive, with low patient survival rates. Overexpression of PME-1 inhibits anoikis in PTEN-deficient prostate cancer cells. The results suggest that PME-1 may be a candidate biomarker for particularly aggressive PTEN-deficient prostate cancer.
MOLECULAR ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Katri Vaparanta, Anne Jokilammi, Ilkka Paatero, Johannes A. Merilahti, Juho Heliste, Karthik Amudhala Hemanthakumar, Riikka Kivela, Kari Alitalo, Pekka Taimen, Klaus Elenius
Summary: In this study, it is demonstrated that Neuregulin-1 (NRG-1) regulates myocardial growth through the STAT5b pathway. Disruption of the NRG-1/ERBB4 pathway or inhibition of Dynamin-2 reduces STAT5b activation and cardiomyocyte hypertrophy. Activation of Stat5 is also observed in NRG-1-induced myocardial growth in zebrafish embryos, and knockdown of stat5b leads to reduced myocardial growth and cardiac function. Furthermore, the NRG-1/ERBB4/STAT5b pathway is differentially regulated in patients with pathological cardiac hypertrophy.
Article
Biology
Johanna Orling, Katri Kosonen, Jenna Villman, Martin Reichard, Ilkka Paatero
Summary: Impaired wound healing associated with aging has significant impacts on human health and healthcare sector. Deficient angiogenesis may contribute to this process, but the underlying biology is still poorly understood due to complexities and costs in using mammalian aging models. In this study, zebrafish and turquoise killifish fin regeneration models were used to investigate aging-related vascular biology of impaired wound healing. The results showed reduced regeneration in the old individuals of both species, accompanied by changes in angiogenesis, vascular density, and expression levels of angiogenesis biomarker VEGF-A. Anti-angiogenic drug SU5416 further reduced regeneration, suggesting the crucial role of angiogenesis in the regeneration of aging caudal fin despite age-related changes in vasculature. These fish fin regeneration models are therefore suitable for studying aging-related decline in wound healing and associated alterations in aging vasculature.
Article
Biochemistry & Molecular Biology
Verneri Virtanen, Kreetta Paunu, Saana Niva, Maria Sundvall, Ilkka Paatero
Summary: Cancer is a significant medical concern and the search for effective treatments continues. This study focuses on caldesmon as a potential novel target for cancer therapy. By analyzing caldesmon mutations in genetically modified zebrafish embryos, the researchers found that these mutations had mild effects on development but altered behavioral responses to light stimuli. Overall, this suggests that caldesmon may be a reasonably well-tolerated target for cancer therapy.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Oncology
Aini Hyytiainen, Katja Korelin, Mervi Toriseva, Tommy Wilkman, Satu Kainulainen, Karri Mesimaki, Johannes Routila, Sami Ventela, Heikki Irjala, Matthias Nees, Ahmed Al-Samadi, Tuula Salo
Summary: This study investigated the changes in gene expression and response to anti-cancer treatments of head and neck squamous cell carcinoma (HNSCC) cells under different culturing conditions. The results showed that culturing conditions can alter the gene expression of cancer cells, and Myogel is more effective at upregulating pathways related to cancer cell proliferation and invasion. The effectiveness of anti-cancer treatments varied depending on the culturing conditions.
CANCER CELL INTERNATIONAL
(2023)
Article
Developmental Biology
Ilkka Paatero
Summary: Power outages can occur at any time and place for various reasons, posing a threat to scientific research in biology. Aquatic animal husbandry, in particular, is vulnerable as the animals' well-being relies on uninterrupted electricity supply, and years of scientific work may be impacted by the condition of these animal stocks. Therefore, it is crucial to have tools for estimating and managing these risks. This study utilizes modeling to assess temperature changes in aquarium water during power outages and develops simplified models for zebrafish facilities. Additionally, a calculation worksheet is provided to assist in modeling the kinetics of water temperature changes.
Article
Multidisciplinary Sciences
Arkadiusz Czerwonka, Joanna Kalafut, Shaoxia Wang, Alinda Anameric, Alicja Przybyszewska-Podstawka, Jesse Mattsson, Mahtab Karbasian, Doriane Le Manach, Mervi Toriseva, Matthias Nees
Summary: This study investigated the effects of different small molecule Notch modulators on head and neck squamous cell carcinoma (HNSCC), compared to the conventional NOTCH interfering compound DAPT. The results showed that RIN-1 had the most pronounced, pleiotropic effects as a Notch modulator. Activation of Notch signaling by RIN-1 led to inhibition of proliferation, growth, and motility of HNSCC cells, as well as induction of cell cycle arrest and apoptosis. Similar anticancer effects were observed in 3D cultures and in the zebrafish model. In contrast, RIN-1 treatment resulted in inhibition of Notch signaling and growth of HNSCC spheroids under non-adherent cell culture conditions.
SCIENTIFIC REPORTS
(2023)