ArticleOncogene2018
Mutant KRAS promotes liver metastasis of colorectal cancer, in part, by upregulating the MEK-Sp1-DNMT1-miR-137-YB-1-IGF-IR signaling pathway.
Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 53 citations in OpenAlex.
- Neural cues differentially modulate colorectal cancer cell behavior depending on patients' genomic background.iScience · 2026Article
- Loss of MicroRNA-29b promotes DNMT3b-mediated STING downregulation to attenuate radiotherapy-induced antitumor immunity in KRAS-mutated colorectal cancer.NPJ precision oncology · 2026Article
- Common oncogenic mutations in colorectal cancer: drivers of carcinogenesis and potential therapeutic targets.Frontiers in pharmacology · 2026Review
- "Paradoxical" prognostic role of the TyG index and a novel machine learning-derived nomogram for colorectal cancer liver metastases.Frontiers in nutrition · 2026Article
- Decitabine promotes degradation of DNMT1 and EZH2 via the ubiquitination pathway and inhibits colorectal cancer progression.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- DNA, RNA, and histone methylation regulation enzymes and their crosstalk in colorectal carcinogenesis and progression: a review of molecular mechanisms, clinical implications, and future perspectives.Cellular & molecular biology letters · 2025Review
- Function ofOncology letters · 2025Review
- Liver metastasis of colorectal cancer: Mechanism and clinical therapy (Review).Oncology reports · 2025Review
- The subcellular distribution of phosphorylated Y-box-binding protein-1 at S102 in colorectal cancer patients, stratified by KRAS mutational status and clinicopathological features.Molecular oncology · 2025Article
- Josephin Domain Containing 2 (JOSD2) inhibition as Pan-KRAS-mutation-targeting strategy for colorectal cancer.Nature communications · 2025Article
- Mortality Outcome Associated with SpecificDiagnostics (Basel, Switzerland) · 2025Article
- Metabolic syndrome in colorectal cancer liver metastasis: metabolic reprogramming and microenvironment crosstalk.Frontiers in immunology · 2025Review
- KRAS inhibitors may prevent colorectal cancer metachronous metastasis by suppressing TGF‑β mediated epithelial‑mesenchymal transition.Molecular medicine reports · 2025Article
- Mechanism of Endogenous Peptide PDYBX1 and Precursor Protein YBX1 in Hirschsprung's Disease.Neuroscience bulletin · 2024Article
- Detecting colorectal cancer using genetic and epigenetic biomarkers: screening and diagnosis.Journal of medicine and life · 2024Review
- Genetic Alterations of NF-κB and Its Regulators: A Rich Platform to Advance Colorectal Cancer Diagnosis and Treatment.International journal of molecular sciences · 2023Review
- Perfluorooctanesulfonic Acid and Perfluorooctanoic Acid Promote Migration of Three-Dimensional Colorectal Cancer Spheroids.Environmental science & technology · 2023Article
- YB-1 activating cascades as potential targets in KRAS-mutated tumors.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2023Review
- A SLC31A1-MEK-DNMT1-miR-124 feedback loop contributes to pancreatic cancer progression.Genes & diseases · 2023Article
- Resistin-like beta reduction is associated to low survival rate and is downregulated by adjuvant therapy in colorectal cancer patients.Scientific reports · 2023Article
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although the role of insulin-like growth factor-I receptor (IGF-IR) in promoting colorectal liver metastasis is known, the mechanism by which IGF-IR is upregulated in colorectal cancer (CRC) is not defined. In this study, we obtained evidence that mutant KRAS transcriptionally activates IGF-IR gene expression through Y-box-binding protein (YB)-1 upregulation via a novel MEK-Sp1-DNMT1-miR-137 pathway in CRC cells. The mechanistic link between the tumor suppressive miR-137 and the translational regulation of YB-1 is intriguing because epigenetic silencing of miR-137 represents an early event in colorectal carcinogenesis due to promoter hypermethylation. This proposed signaling axis was further verified by the immunohistochemical evaluations of liver metastases from a cohort of 46 KRAS mutant CRC patients, which showed a significant correlation in the expression levels among Sp1, miR-137, YB-1, and IGF-1R. Moreover, suppression of the expression of YB-1 and IGF-IR via genetic knockdown or the pharmacological inhibition of MEK hampers KRAS-driven colorectal liver metastasis in our animal model studies. From a translational perspective, the identification of this KRAS-driven pathway might provide a mechanistic rationale for the use of a MEK inhibitor as an adjuvant, in combination with standard of care, to prevent the recurrence of colorectal liver metastasis in KRAS mutant CRC patients after receiving liver resection, which warrants further investigation.
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