ArticleBMC cancer2018
WDR5 supports colon cancer cells by promoting methylation of H3K4 and suppressing DNA damage.
Article in BMC cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 55 citations in OpenAlex.
- Article
- Epigenetic compartmentalization of mitotic chromosomes by phase-separation-driven repulsion between WDR5 and the chromosomal passenger complex.Nature communications · 2026Article
- Chromatin Regulatory Targets for Anticancer Therapeutics.Chemical reviews · 2025Review
- Review
- Targeting MLL1/WDR5-Mediated Epigenetic Regulation Mitigates Peritoneal Fibrosis by Reducing p16FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Article
- Article
- The COMPASS complex maintains the metastatic capacity imparted by a subpopulation of cells in UPS.iScience · 2024Article
- Transcription elongation defects link oncogenic SF3B1 mutations to targetable alterations in chromatin landscape.Molecular cell · 2024Article
- Unannotated microprotein EMBOW regulates the interactome and chromatin and mitotic functions of WDR5.Cell reports · 2023Article
- A novel TOX3-WDR5-ABCG2 signaling axis regulates the progression of colorectal cancer by accelerating stem-like traits and chemoresistance.PLoS biology · 2023Article
- PROTACs in Epigenetic Cancer Therapy: Current Status and Future Opportunities.Molecules (Basel, Switzerland) · 2023Review
- Structure-based discovery of potent WD repeat domain 5 inhibitors that demonstrate efficacy and safety in preclinical animal models.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- DPY30 Promotes Proliferation and Cell Cycle Progression of Colorectal Cancer Cells via Mediating H3K4 Trimethylation.International journal of medical sciences · 2023Article
- RhoC in association with TET2/WDR5 regulates cancer stem cells by epigenetically modifying the expression of pluripotency genes.Cellular and molecular life sciences : CMLS · 2022Article
- WIN site inhibition disrupts a subset of WDR5 function.Scientific reports · 2022Article
- USP44 accelerates the growth of T-cell acute lymphoblastic leukemia through interacting with WDR5 and repressing its ubiquitination.International journal of medical sciences · 2022Article
- MKL1 regulates hepatocellular carcinoma cell proliferation, migration and apoptosis via the COMPASS complex and NF-κB signaling.BMC cancer · 2021Article
- Targeting WD repeat domain 5 enhances chemosensitivity and inhibits proliferation and programmed death-ligand 1 expression in bladder cancer.Journal of experimental & clinical cancer research : CR · 2021Article
- Structural insights into the recognition of histone H3Q5 serotonylation by WDR5.Science advances · 2021Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundKMT2/MLL proteins are commonly overexpressed or mutated in cancer and have been shown to support cancer maintenance. These proteins are responsible for methylating histone 3 at lysine 4 and promoting transcription and DNA synthesis; however, they are inactive outside of a multi-protein complex that requires WDR5. WDR5 has been implicated in cancer for its role in the COMPASS complex and its interaction with Myc; however, the role of WDR5 in colon cancer has not yet been elucidated.
methodsWDR5 expression was evaluated using RT-qPCR and western blot analysis. Cell viability and colony forming assays were utilized to evaluate the effects of WDR5 depletion or inhibition in colon cancer cells. Downstream effects of WDR5 depletion and inhibition were observed by western blot.
resultsWDR5 is overexpressed in colon tumors and colon cancer cell lines at the mRNA and protein level. WDR5 depletion reduces cell viability in HCT116, LoVo, RKO, HCT15, SW480, SW620, and T84 colon cancer cells. Inhibition of the WDR5:KMT2/MLL interaction using OICR-9429 reduces cell viability in the same panel of cell lines albeit not to the same extent as RNAi-mediated WDR5 depletion. WDR5 depletion reduced H3K4Me3 and increased phosphorylation of H2AX in HCT116, SW620, and RKO colon cancer cells; however, OICR-9429 treatment did not recapitulate these effects in all cell lines potentially explaining the reduced toxicity of OICR-9429 treatment as compared to WDR5 depletion. WDR5 depletion also sensitized colon cancer cells to radiation-induced DNA damage.
conclusionsThese data demonstrate a clear role for WDR5 in colon cancer and future studies should examine its potential to serve as a therapeutic target in cancer. Additional studies are needed to fully elucidate if the requirement for WDR5 is independent of or consistent with its role within the COMPASS complex. OICR-9429 treatment was particularly toxic to SW620 and T84 colon cancer cells, two cell lines without mutations in WDR5 and KMT2/MLL proteins suggesting COMPASS complex inhibition may be particularly effective in tumors lacking KMT2 mutations. Additionally, the ability of WDR5 depletion to amplify the toxic effects of radiation presents the possibility of targeting WDR5 to sensitize cells to DNA-damaging therapies.
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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.