ArticleOncogene2013
The histone methyltransferase MMSET/WHSC1 activates TWIST1 to promote an epithelial-mesenchymal transition and invasive properties of prostate cancer.
Article in Oncogene, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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Who cites it
95 citing papers in PubMed, 159 citations in OpenAlex.
- The Spectrum and Clinical Impact of Epigenetic Modifier Mutations in Myeloma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Trial
- Review
- Article
- NSD Family-Mediated H3K36 Methylation in Human Cancer: Mechanisms and Therapeutic Opportunities.Biomedicines · 2025Review
- Review
- Opposite patterns of association of TWIST1 expression with patient survival in SHH and Group 4 medulloblastoma.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2025Article
- H3K36me2 methyltransferase NSD2/WHSC1 promotes triple-negative breast cancer metastasis via activation of ULK1-dependent autophagy.Autophagy · 2025Article
- Urinary Extracellular Vesicle Signatures as Biomarkers in Prostate Cancer Patients.International journal of molecular sciences · 2025Article
- NASP implication in the androgen receptor associated with castration resistance in prostate cancer.Cell communication and signaling : CCS · 2025Article
- Histone-modifying enzymes as drivers and therapeutic targets in androgen-resistant prostate cancer.Frontiers in endocrinology · 2025Review
- Novel dual-targeting inhibitors of NSD2 and HDAC2 for the treatment of liver cancer: structure-based virtual screening, molecular dynamics simulation, andJournal of enzyme inhibition and medicinal chemistry · 2024Article
- NSD2 is a requisite subunit of the AR/FOXA1 neo-enhanceosome in promoting prostate tumorigenesis.Nature genetics · 2024Article
- Review
- Multilevel Regulation of NF-κB Signaling by NSD2 Suppresses Kras-Driven Pancreatic Tumorigenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Article
- NSD family proteins: Rising stars as therapeutic targets.Cell insight · 2024Review
- NSD2 is a requisite subunit of the AR/FOXA1 neo-enhanceosome in promoting prostate tumorigenesis.bioRxiv : the preprint server for biology · 2024Article
- Association of WHSC1/NSD2 and T-cell infiltration with prostate cancer metastasis and prognosis.Scientific reports · 2023Article
- Drug Discovery Targeting Nuclear Receptor Binding SET Domain Protein 2 (NSD2).Journal of medicinal chemistry · 2023Review
- Targeting SphK1/2 by SKI-178 inhibits prostate cancer cell growth.Cell death & disease · 2023Article
35 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Epigenetic deregulation of gene expression has a role in the initiation and progression of prostate cancer (PCa). The histone methyltransferase MMSET/WHSC1 (Multiple Myeloma SET domain) is overexpressed in a number of metastatic tumors, but its mechanism of action has not been defined. In this work, we found that PCa cell lines expressed significantly higher levels of MMSET compared with immortalized, non-transformed prostate cells. Knockdown experiments showed that, in metastatic PCa cell lines, dimethylation of lysine 36 and trimethylation of lysine 27 on histone H3 (H3K36me2 and H3K27me3, respectively) depended on MMSET expression, whereas depletion of MMSET in benign prostatic cells did not affect chromatin modifications. Knockdown of MMSET in DU145 and PC-3 tumor cells decreased cell proliferation, colony formation in soft agar and strikingly diminished cell migration and invasion. Conversely, overexpression of MMSET in immortalized, non-transformed RWPE-1 cells promoted cell migration and invasion, accompanied by an epithelial-mesenchymal transition (EMT). Among a panel of EMT-promoting genes analyzed, TWIST1 expression was strongly activated in response to MMSET. Chromatin immunoprecipitation analysis demonstrated that MMSET binds to the TWIST1 locus and leads to an increase in H3K36me2, suggesting a direct role of MMSET in the regulation of this gene. Depletion of TWIST1 in MMSET-overexpressing RWPE-1 cells blocked cell invasion and EMT, indicating that TWIST1 was a critical target of MMSET, responsible for the acquisition of an invasive phenotype. Collectively, these data suggest that MMSET has a role in PCa pathogenesis and progression through epigenetic regulation of metastasis-related genes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.