Oral squamous cell carcinoma (OSCC) is a malignancy all over the world. WD repeat domain 5 (WDR5) is involved in cancer progression. In addition, it was reported that WDR5 is upregulated in head and neck cancer, while its role in OSCC is unknown. First, the expression of WDR5 in oral cancer tissues and cells was examined by qRT-PCR, IHF and western blot. CCK-8 assay was performed to test the cell viability. Cell migration was assessed by transwell assay. Knocking down WDR5 or CARM1 in oral cancer cells to detect its function on cancer growth, WDR5 and CARM1 were significantly upregulated in OSCC. Silencing WDR5 suppressed OSCC cell viability and migration. CARM1 level in OSCC cells was significantly inhibited by WDR5 downregulation, and CARM1 elevation could rescue the effect of WDR5 knockdown on tumorigenesis of OSCC. Moreover, silencing of WDR5 notably inactivated β-catenin signaling pathway, while this phenomenon was restored by CARM1 overexpression. Silencing of WDR5 attenuated the tumorigenesis of OSCC via CARM1/β-catenin axis. Thus, WDR5 might be a target for OSCC treatment.
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http://dx.doi.org/10.1007/s10266-021-00649-6 | DOI Listing |
Expert Opin Ther Pat
January 2025
Center for Therapeutics Discovery, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Introduction: WDR5 is an epigenetic scaffolding protein that has attracted significant interest as an anti-cancer drug target, especially in MLL-rearranged leukemias. The most druggable 'WIN-site' on WDR5, which tethers WDR5 to chromatin, has been successfully targeted with multiple classes of exquisitely potent small-molecule protein-protein interaction inhibitors. Earlier progress has also been made on the development of WDR5 degraders and inhibitors at the 'WBM-site' on the opposite face of WDR5.
View Article and Find Full Text PDFSci Adv
December 2024
Laboratory of Cell Cycle Regulation, Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad 500039, India.
Dysfunction of the centrosome, the major microtubule-organizing center of the cell, is implicated in microcephaly. Haploinsufficiency of mixed-lineage leukemia (MLL/KMT2A) protein causes Wiedemann-Steiner syndrome (WSS), a neurodevelopmental disorder associated with microcephaly. However, whether MLL has a function at the centrosome is not clear.
View Article and Find Full Text PDFAm J Cancer Res
November 2024
Department of Laboratory Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine Shanghai, China.
Elevated subcutaneous adipose tissue in obese men correlates strongly with a higher risk of aggressive prostate cancer and poor treatment outcomes, but the exact mechanism underlying the increased risk remains elusive. To address this question, we analyzed prostate cancer transcriptomic data from The Cancer Genome Atlas as well as single-cell RNA sequencing and tissue microarray data from prostate cancer cells. Subcutaneous adipose tissue-associated cysteine-rich protein 2 (CSRP2) was significantly downregulated in prostate cancer epithelial cells.
View Article and Find Full Text PDFElife
December 2024
Institute of Biochemistry, University of Kiel, Kiel, Germany.
The development of proteolysis targeting chimeras (PROTACs), which induce the degradation of target proteins by bringing them into proximity with cellular E3 ubiquitin ligases, has revolutionized drug development. While the human genome encodes more than 600 different E3 ligases, current PROTACs use only a handful of them, drastically limiting their full potential. Furthermore, many PROTAC development campaigns fail because the selected E3 ligase candidates are unable to induce degradation of the particular target of interest.
View Article and Find Full Text PDFBioorg Chem
November 2024
Institute of Pharmacology & Toxicology, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, PR China; Innovation Institute for Artificial Intelligence in Medicine of Zhejiang University, Hangzhou 310018, PR China; Engineering Research Center of Innovative Anticancer Drugs, Ministry of Education, Hangzhou 310058, PR China. Electronic address:
WD repeat-containing protein 5 (WDR5) is a scaffolding protein involved in critical protein-protein interactions and a promising target for therapeutic development. Novel small-molecule ligands targeting WDR5 were identified using the DELopen platform, a free-access DNA-encoded chemical library (DEL) for academic research. Through off-DNA structure-activity relationship studies and photoaffinity labeling, two promising initial leads, DBL-6-13 and DBL-6-33, were identified as new binders of WDR5.
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