The use of androgen receptor (AR) inhibitors in prostate cancer gives rise to increased cellular lineage plasticity resulting in resistance to AR-targeted therapies. In this study, we examined the chromatin landscape of AR-positive prostate cancer cells post-exposure to the AR inhibitor enzalutamide. We identified a novel regulator of cell plasticity, the homeobox transcription factor SIX2, whose motif is enriched in accessible chromatin regions after treatment. Depletion of SIX2 in androgen-independent PC-3 prostate cancer cells induced a switch from a stem-like to an epithelial state, resulting in reduced cancer-related properties such as proliferation, colony formation, and metastasis both in vitro and in vivo. These effects were mediated through the downregulation of the Wnt/β-catenin signalling pathway and subsequent reduction of nuclear β-catenin. Collectively, our findings provide compelling evidence that the depletion of SIX2 may represent a promising strategy for overcoming the cell plasticity mechanisms driving antiandrogen resistance in prostate cancer.
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http://dx.doi.org/10.1093/nar/gkae206 | DOI Listing |
J Biochem Mol Toxicol
January 2025
Department of Translational Medicine, Clinical Research Centre, Skåne University Hospital, Lund University, Malmö, Sweden.
Berberine, an isoquinoline alkaloid derived from various medicinal plants, emerges as a potential therapeutic agent against diverse human diseases. It has particularly shown notable anticancer efficacy against breast, colorectal, lung, prostate, and liver cancer. Berberine results in inhibition of cancer cell proliferation, induction of apoptosis, and suppressing angiogenesis, positioning it as a versatile, multitargeted therapeutic tool against cancer.
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December 2024
Department of Community Health, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.
Background: Prostate cancer is a common cancer among men globally and its treatment affects quality of life. Poor patients' perception of prostate cancer services may lead to their late presentation for care, often presenting with the advanced stage of the disease. This may vary from one region to another.
View Article and Find Full Text PDFFront Oncol
December 2024
Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia.
Prostate cancer is a common malignancy with an increasing incidence in ageing populations. However, older patients with prostate cancer are often underrepresented in traditional clinical trials. The electronic Prostate Cancer Australian and Asian Database (ePAD) is a multi-centre, multi-national prospective clinical registry, that records real world data from a broader population.
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December 2024
Department of Biomedical Informatics, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
CHD6, a member of the chromodomain helicase DNA-binding protein family, has been implicated in various diseases and tumors. However, its precise binding model of CHD6 on regulatory functional genes remains poorly understood. In this study, we discovered sharp peaks of CHD6, as the first member of CHD family for housekeeping process, binding only to the promoter region of genes in the C4-2 cell line.
View Article and Find Full Text PDFPhys Imaging Radiat Oncol
October 2024
Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
Purpose: Multiparametric magnetic resonance imaging (MRI) is known to provide predictors for malignancy and treatment outcome. The inclusion of these datasets in workflows for online adaptive planning remains under investigation. We demonstrate the feasibility of longitudinal relaxometry in online MR-guided adaptive stereotactic body radiotherapy (SBRT) to the prostate and dominant intra-prostatic lesion (DIL).
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