Article
Biology
Wei-Yu Chen, Yu-Ching Wen, Shian-Ren Lin, Hsiu-Lien Yeh, Kuo-Ching Jiang, Wei-Hao Chen, Yow-Sien Lin, Qingfu Zhang, Phui-Ly Liew, Michael Hsiao, Jiaoti Huang, Yen-Nien Liu
Summary: The study reveals that NGF, upregulated by transcription factor ZBTB46 in prostate cancer exposed to androgen therapy, promotes neuroendocrine differentiation. NGF interacts with GPCR CHRM4, both of which are upregulated in highly metastatic prostate cancer, and targeting NGF reduces therapy resistance in a mouse xenograft model.
COMMUNICATIONS BIOLOGY
(2021)
Article
Oncology
Jing Wei, Lijuan Yin, Jingjing Li, Jing Wang, Tianjie Pu, Peng Duan, Tzu-Ping Lin, Allen C. Gao, Boyang Jason Wu
Summary: The study reveals a reciprocal regulatory circuit between MAOA and AR in prostate cancer, with implications for cancer development and growth, particularly CRPC. Targeting MAOA may enhance the efficacy of AR-targeted therapies.
Article
Immunology
Ji-Hak Jeong, Shangwei Zhong, Fuzhuo Li, Changhao Huang, Xueyan Chen, Qingqing Liu, Shoujiao Peng, HaJeung Park, You Mie Lee, Jasreman Dhillon, Jun-Li Luo
Summary: This study reveals that OBP2A released from PCa in remission during ADT interacts with CXCL15/IL8, leading to enhanced PCa growth and MDSCs infiltration, which contributes to the emergence of castration resistance. Targeting OBP2A of tumor in remission would be an effective therapeutic strategy for advanced PCa.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Oncology
Junjiang Liu, Yunxia Zhang, Shoubin Li, Fuzhen Sun, Gang Wang, Dong Wei, Tao Yang, Shouyi Gu
Summary: Androgen deprivation therapy (ADT) can increase the expression of androgen receptor (AR) through amplification of chromosome X in prostate cancer. The overexpression of OPHN1, which is located in the same region as the AR gene, was found to promote cell survival, inhibit apoptosis, and enhance resistance to ADT, thereby facilitating prostate cancer progression.
Article
Oncology
Kumar Nikhil, Hanan S. Haymour, Mohini Kamra, Kavita Shah
Summary: This study identified that LIMK2 degrades SPOP by direct phosphorylation and creates a feedback loop to promote oncogenicity in prostate cancer. Understanding the relationship between LIMK2 and SPOP provides a powerful opportunity to inhibit LIMK2 and retain WT-SPOP, effectively halting disease progression.
BRITISH JOURNAL OF CANCER
(2021)
Article
Cell Biology
Dingheng Lu, Yarong Song, Ying Yu, Decai Wang, Bing Liu, Liang Chen, Xuexiang Li, Yunxue Li, Lulin Cheng, Fang Lv, Pu Zhang, Yifei Xing
Summary: Abiraterone, a novel androgen synthesis inhibitor, is approved for treating castration-resistant prostate cancer(CRPC). However, patients often develop resistance to it, and the role of Lysine acetyltransferase 2 A (KAT2A) in this resistance was investigated. Higher KAT2A expression was found in abiraterone-resistant prostate cancer cells and in patients with poor clinical outcomes. Knocking down KAT2A partially resensitized resistant cells to abiraterone, while overexpressing it promoted resistance. These findings suggest KAT2A as a potential target for CRPC treatment.
CELL DEATH & DISEASE
(2021)
Editorial Material
Cell Biology
Li Xin
Summary: A recent study by Steiner et al. reveals that Ly6d(+) prostate tumor cells can survive after castration through an autocrine amphiregulin signaling pathway.
TRENDS IN CELL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Wei Liu, Chunyu Wang, Shengli Wang, Kai Zeng, Shan Wei, Ning Sun, Ge Sun, Manlin Wang, Renlong Zou, Wensu Liu, Lin Lin, Huijuan Song, Zining Jin, Yue Zhao
Summary: PRPF6 plays a key role in enhancing the actions of AR full length and variant 7 in prostate cancer, promoting AR-induced transactivation and tumor growth, as well as being highly expressed in human prostate cancer samples.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2021)
Article
Oncology
Fen Ma, Seiji Arai, Keshan Wang, Carla Calagua, Amanda R. Yuan, Larysa Poluben, Zhongkai Gu, Joshua W. Russo, David J. Einstein, Huihui Ye, Meng Xiao He, Yu Liu, Eliezer Van Allen, Adam G. Sowalsky, Manoj K. Bhasin, Xin Yuan, Steven P. Balk
Summary: This study reveals the importance of Wnt/beta-catenin signaling in prostate cancer, showing its role in stem cell maintenance and invasion. It identifies new effectors and drivers of this pathway in prostate cancer, such as ROR1 and APC genomic loss. The findings suggest that targeting Wnt/beta-catenin signaling may be a potential therapeutic strategy for prostate cancer.
Review
Biochemistry & Molecular Biology
David Ka-Wai Leung, Peter Ka-Fung Chiu, Chi-Fai Ng, Jeremy Yuen-Chun Teoh
Summary: The management of castration-resistant prostate cancer has seen significant progress, with three novel hormonal agents showing survival benefits in non-metastatic patients and a wider range of management options being investigated for metastatic disease.
Article
Engineering, Biomedical
Nicole L. Habbit, Benjamin Anbiah, Joshita Suresh, Luke Anderson, Megan L. Davies, Iman Hassani, Taraswi M. Ghosh, Michael W. Greene, Balabhaskar Prabhakarpandian, Robert D. Arnold, Elizabeth A. Lipke
Summary: Using a 3D-engineered prostate cancer (PCa) tissue model, this study reveals that the incorporation of fibroblasts promotes PCa aggression by increasing proliferation, significant matrix remodeling, and enrichment of tumorigenic hallmark gene sets. Fibroblasts play an elevated role in indolent disease states and may contribute to the switch from androgen-dependent to castration-resistant PCa.
ADVANCED HEALTHCARE MATERIALS
(2023)
Article
Oncology
Zoila A. Lopez-Bujanda, Michael C. Haffner, Matthew G. Chaimowitz, Nivedita Chowdhury, Nicholas J. Venturini, Radhika A. Patel, Aleksandar Obradovic, Corey S. Hansen, Joanna Jackow, Janielle P. Maynard, Karen S. Sfanos, Cory Abate-Shen, Charles J. Bieberich, Paula J. Hurley, Mark J. Selby, Alan J. Korman, Angela M. Christiano, Angelo M. De Marzo, Charles G. Drake
Summary: Castration increases IL-8 expression in prostate epithelial cells, leading to infiltration of tumor-promoting PMN-MDSCs, which can be mitigated by blocking IL-8 signaling. Targeting IL-8 signaling in combination with ICB delays castration resistance and increases polyfunctional CD8 T cell density in tumors.
Article
Neurosciences
Maud Gratuze, Johannes C. M. Schlachetzki, Ricardo D'Oliveira Albanus, Nimansha Jain, Brenna Novotny, Logan Brase, Lea Rodriguez, Clayton Mansel, Michal Kipnis, Sydney O'Brien, Martina P. Pasillas, Choonghee Lee, Melissa Manis, Marco Colonna, Oscar Harari, Christopher K. Glass, Jason D. Ulrich, David M. Holtzman
Summary: In addition to tau and Ab pathologies, inflammation and variants in APOE and TREM2 play important roles in Alzheimer's disease (AD). This study explores the relationship between microgliosis and tau-mediated neurodegeneration in the presence of ApoE4. Surprisingly, the knockout of TREM2 exacerbates neurodegeneration and tau pathology, suggesting that tau pathology-dependent microgliosis facilitates neurodegeneration in the presence of ApoE4.
Review
Medicine, General & Internal
Shangwei Zhong, Changhao Huang, Zhikang Chen, Zihua Chen, Jun-Li Luo
Summary: Castration-resistant prostate cancer (CRPC) develops from the transformation of androgen-dependent (AD) prostate cancer (PCa) to androgen-independent (AI) PCa under androgen deprivation therapy (ADT). This forced evolutionary process allows AI PCa cells to selectively and dominantly proliferate, making PCa cells and the tumor microenvironment (TME) adapt and reprogram under ADT. Currently, there are no effective therapeutic methods available for the treatment of CRPC, highlighting the importance of targeting inflammatory signaling for the emergence and maintenance of CRPC.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Medicine, Research & Experimental
Sue Jin Moon, Byong Chang Jeong, Hwa Jin Kim, Joung Eun Lim, Hye-Jeong Kim, Ghee Young Kwon, Joshua A. Jackman, Jeong Hoon Kim
Summary: The study identified BCT as a potent inhibitor targeting both AR-FL and AR-V7 activities in CRPC, effectively suppressing tumor growth and metastasis. Mechanistically, BCT disrupts the interaction of HSP90 with AR-FL/AR-V7, leading to their degradation and showing promising therapeutic potential against CRPC.
Article
Cell Biology
Sirin Saranyutanon, Srijan Acharya, Sachin Kumar Deshmukh, Mohammad Aslam Khan, Seema Singh, Ajay Pratap Singh
Summary: Nicotine induces M2 polarization of macrophages, enhancing their growth, motility, and invasion, potentially through the Src-STAT3 signaling axis. This novel role of nicotine in immunosuppression could be implicated in the pathogenesis of various diseases.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Multidisciplinary Sciences
Alyson Nguyen, Keith Battle, Sunita S. Paudel, Ningyong Xu, Jessica Bell, Linn Ayers, Cassandra Chapman, Ajay P. Singh, Srinivas Palanki, Thomas Rich, Diego F. Alvarez, Troy Stevens, Dhananjay T. Tambe
Summary: Quantitative assessment of cellular forces and motion has made significant progress in the past four decades. However, the field currently faces challenges in data standardization, data analysis and visualization, and accessibility for common cell biology laboratories. To address these limitations, a new experimental platform called Integrative Toolkit to Analyze Cellular Signals (iTACS) has been developed. iTACS consists of two components, namely Acquisition and Training Module (AcTrM) and Analysis and Visualization Module (AnViM). AcTrM facilitates user self-training and automation of image acquisition protocols, while AnViM provides user-friendly automation of data analysis and visualization. The platform enables the analysis of various properties and offers solutions for data standardization and user-friendly analysis without requiring an engineering background.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2022)
Article
Biochemistry & Molecular Biology
Shashi Anand, Mohammad Aslam Khan, Haseeb Zubair, Sarabjeet Kour Sudan, Kunwar Somesh Vikramdeo, Sachin Kumar Deshmukh, Shafquat Azim, Sanjeev Kumar Srivastava, Seema Singh, Ajay Pratap Singh
Summary: Extensive desmoplasia and poor vasculature contribute to the aggressiveness and therapy resistance of pancreatic tumors by causing severe hypoxia. In this study, we identify the HuR/MYB/HIF1 alpha axis as a critical regulator of the metabolic plasticity and hypoxic survival of pancreatic cancer cells. HuR translocates from the nuclear to the cytoplasm under hypoxia and stabilizes MYB transcripts, which in turn upregulates HIF1 alpha transcriptionally. MYB promotes the transcription of multiple HIF1 alpha-regulated glycolytic genes by binding directly to their promoters, thus enhancing HIF1 alpha recruitment to hypoxia-responsive elements through interaction with p300-dependent histone acetylation. Depletion of MYB significantly reduces tumorigenic ability, glucose uptake, and metabolism in orthotopic mouse models of pancreatic cancer, even after the restoration of HIF1 alpha. These findings highlight the essential role of MYB in the metabolic reprogramming that supports the survival of pancreatic cancer cells under hypoxia.
Review
Biochemistry & Molecular Biology
Mary Oluwadamilola Haastrup, Kunwar Somesh Vikramdeo, Seema Singh, Ajay Pratap Singh, Santanu Dasgupta
Summary: Mitochondria are vital organelles involved in various cellular functions. They have their own genome and machinery for synthesizing essential proteins, while the majority of the proteins are produced in the cytosol and imported into mitochondria. Proper functioning of the mitochondrial protein import system is crucial for mitochondrial and cellular homeostasis. Impaired protein import can lead to proteotoxic stress and altered mitochondrial unfolded protein response, which are associated with various diseases. This review highlights the mechanisms of nuclear-encoded mitochondrial protein import, the consequences of defective import, and the pathological conditions associated with altered unfolded protein response.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Srijan Acharya, Shashi Anand, Mohammad Aslam Khan, Haseeb Zubair, Sanjeev Kumar Srivastava, Seema Singh, Ajay Pratap Singh
Summary: MYB, a proto-oncogene, is overexpressed in prostate cancer and promotes its growth, aggressiveness, and resistance to androgen-deprivation therapy. Androgen signaling regulates MYB expression through transcriptional upregulation mediated by androgen receptor binding to the MYB promoter. High-dose androgen treatment leads to decreased MYB stability and induction of miR-150, which suppresses MYB expression and PCa cell growth.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Editorial Material
Oncology
Amod Sharma, Ajay Pratap Singh, Seema Singh
Editorial Material
Oncology
Shashi Anand, Mohammad Aslam Khan, Ajay Pratap Singh
Review
Biochemistry & Molecular Biology
Poornima Verma, Neha Shukla, Shivani Kumari, M. S. Ansari, Naveen Kumar Gautam, Girijesh Kumar Patel
Summary: Prostate cancer is the most common malignancy in men worldwide. Cancer stem cells, which possess unique properties and are responsible for therapy resistance and disease relapse in several malignancies including prostate cancer, can be identified by certain markers such as ALDH EZH2, OCT4, SOX2, c-MYC, and Nanog. Advances in the field offer explanations for uncertainties surrounding the etiology and hope for the development of new stem-cell targets and efficient therapies in the future. This review discusses the identification, properties, pathways, diagnostics, and interventions of prostate cancer stem cells.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2023)
Review
Biochemistry & Molecular Biology
Kunwar Somesh Vikramdeo, Amod Sharma, Shashi Anand, Sarabjeet Kour Sudan, Seema Singh, Ajay Pratap Singh, Santanu Dasgupta
Summary: Prostate cancer is a major cause of cancer-related mortality globally, and race-associated health disparities are common and concerning. PSA-based screening is commonly used for early diagnosis, but it cannot distinguish between indolent and aggressive prostate cancer. Androgen or androgen receptor-targeted therapies are standard treatments, but resistance is common. Mitochondrial alterations are common in prostate cancer and affect tumor-supportive stromal remodeling. This article discusses the role of mitochondrial alterations in prostate cancer pathobiology, therapy resistance, and racial disparities, as well as their potential as prognostic biomarkers and therapeutic targets.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Sooraj Kakkat, Paramahansa Pramanik, Seema Singh, Ajay Pratap Singh, Chandrani Sarkar, Debanjan Chakroborty
Summary: Cardiovascular diseases (CVDs) and complications are commonly observed in patients with prostate cancer (PCa) and can impact their clinical management. Androgen deprivation therapy (ADT), the main treatment for PCa, has been shown to increase cardiovascular risks and metabolic syndromes. There is emerging evidence of a molecular link between PCa and CVDs, but it remains to be fully understood. This article explores the connection between PCa and CVDs, utilizing a comprehensive gene expression study and biological pathway analysis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Editorial Material
Cell Biology
Girijesh Kumar Patel, Santosh Kumar Verma, Shagun Misra, Gyan Chand, Ram Nawal Rao
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Kunwar Somesh Vikramdeo, Shashi Anand, Sarabjeet Kour Sudan, Paramahansa Pramanik, Seema Singh, Andrew K. Godwin, Ajay Pratap Singh, Santanu Dasgupta
Summary: This study aimed to develop mitochondrial DNA (mtDNA)-based liquid biomarkers for early detection and recurrence prediction in triple-negative breast cancer (TNBC) patients. The study identified hotspot mtDNA mutations in serum-derived extracellular vesicles (EVs) of TNBC patients, which could be potentially used for noninvasive detection. Additionally, the study found that women with African ancestry had higher mtDNA mutation load. The detection of tumor-specific mtDNA mutations and measurement of mtDNA and cardiolipin (CL) contents in EVs could be valuable for noninvasive early detection and recurrence prediction strategies.