ArticleMolecular cancer2021
A new KSRP-binding compound suppresses distant metastasis of colorectal cancer by targeting the oncogenic KITENIN complex.
Article in Molecular cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 25 citations in OpenAlex.
- Review
- Epigenetic Silencing of miR-124 Drives KITENIN Activation in Colorectal Cancer.Biomolecules & therapeutics · 2026Article
- A three-gene radioresistance signature predicts tumor progression in cervical cancer.Translational cancer research · 2026Article
- Review
- A novel small molecule inhibitor targeting KHSRP methylation suppresses colon cancer progression.Acta pharmaceutica Sinica. B · 2026Article
- Targeting KITENIN signaling in cancer progression and therapeutic resistance: mechanistic insights and future directions.Cancer cell international · 2026Review
- KITENIN-CCL20 axis is a potential therapeutic target for modulating immunosuppressive tumor microenvironment in glioblastoma.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- KSRP-mediated Wnt/β-catenin activation promotes follicular thyroid cancer progression and stemness.British journal of cancer · 2025Article
- Diarylpentanoid, a curcumin analog, inhibits malignant meningioma growth in bothWorld journal of experimental medicine · 2025Article
- K-Homology Splicing Regulatory Protein (KSRP) Augments Survival and Proliferation of Human Melanoma Cells.Current issues in molecular biology · 2025Article
- Dynamic changes in immune cells in humanized liver metastasis and subcutaneous xenograft mouse models.Scientific reports · 2024Article
- Chrysophanol inhibits of colorectal cancer cell motility and energy metabolism by targeting the KITENIN/ErbB4 oncogenic complex.Cancer cell international · 2024Article
- Usnic Acid Targets 14-3-3 Proteins and Suppresses Cancer Progression by Blocking Substrate Interaction.JACS Au · 2024Article
- Anithiactin D, a Phenylthiazole Natural Product from Mudflat-DerivedMarine drugs · 2024Article
- K-Homology Type Splicing Regulatory Protein: Mechanism of Action in Cancer and Immune Disorders.Critical reviews in eukaryotic gene expression · 2024Article
- KITENIN promotes aerobic glycolysis through PKM2 induction by upregulating the c-Myc/hnRNPs axis in colorectal cancer.Cell & bioscience · 2023Article
- Enhancer RNA promotes resistance to radiotherapy in bone-metastatic prostate cancer by mTheranostics · 2023Article
- A peptide interfering with the dimerization of oncogenic KITENIN protein and its stability suppresses colorectal tumour progression.Clinical and translational medicine · 2022Article
- Nomogram predicting the cancer-specific survival of early-onset colorectal cancer patients with synchronous liver metastasis: a population-based study.International journal of colorectal disease · 2022Article
- The Role of KH-Type Splicing Regulatory Protein (KSRP) for Immune Functions and Tumorigenesis.Cells · 2022Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDistant metastasis is the major cause of death in patients with colorectal cancer (CRC). Previously, we identified KITENIN as a metastasis-enhancing gene and suggested that the oncogenic KITENIN complex is involved in metastatic dissemination of KITENIN-overexpressing CRC cells. Here, we attempted to find substances targeting the KITENIN complex and test their ability to suppress distant metastasis of CRC.
methodsWe screened a small-molecule compound library to find candidate substances suppressing the KITENIN complex in CRC cells. We selected a candidate compound and examined its effects on the KITENIN complex and distant metastasis through in vitro assays, a molecular docking model, and in vivo tumor models.
resultsAmong several compounds, we identified DKC1125 (Disintegrator of KITENIN Complex #1125) as the best candidate. DKC1125 specifically suppressed KITENIN gain of function. After binding KH-type splicing regulatory protein (KSRP), DKC1125 degraded KITENIN and Dvl2 by recruiting RACK1 and miRNA-124, leading to the disintegration of the functional KITENIN-KSRP-RACK1-Dvl2 complex. A computer docking model suggested that DKC1125 specifically interacted with the binding pocket of the fourth KH-domain of KSRP. KITENIN-overexpressing CRC cells deregulated certain microRNAs and were resistant to 5-fluorouracil, oxaliplatin, and cetuximab. DKC1125 restored sensitivity to these drugs by normalizing expression of the deregulated microRNAs, including miRNA-124. DKC1125 effectively suppressed colorectal liver metastasis in a mouse model. Interestingly, the combination of DKC1125 with 5-fluorouracil suppressed metastasis more effectively than either drug alone.
conclusionDKC1125 targets the KITENIN complex and could therefore be used as a novel therapeutic to suppress liver metastasis in CRC expressing high levels of KITENIN.
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