ArticleOncogenesis2019
An FBXW7-ZEB2 axis links EMT and tumour microenvironment to promote colorectal cancer stem cells and chemoresistance.
Article in Oncogenesis, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
104 citing papers in PubMed, 1 synthesis or guideline pooled it, 145 citations in OpenAlex.
- FBXW7 Gene Mutation and Expression in Colorectal Cancer (CRC): A Systematic Review from Molecular Mechanisms to Clinical Translation.International journal of molecular sciences · 2025Pooled it
- The ADAP-TRIM21-ZEB2 axis regulates CD8iScience · 2026Article
- Translational insights and clinical challenges of targeting cancer stem cells.Signal transduction and targeted therapy · 2026Review
- Multi-omics analysis of patient-derived organoids reveals that E3 ligase COP1 promotes liver metastasis and oxaliplatin resistance in colorectal cancer through LUZP1 degradation and MYL9 phosphorylation.Experimental hematology & oncology · 2026Article
- Class IIa HDACs forced degradation allows resensitization of oxaliplatin-resistant FBXW7-mutated colorectal cancer.Molecular oncology · 2026Article
- FBXW7 suppresses cell proliferation, migration, and epithelial-mesenchymal transition in endometrioid ovarian carcinoma.Journal of Cancer · 2026Article
- An epithelial-mesenchymal transition-related gene signature predicts prognosis, immune infiltration, and drug sensitivity in colorectal cancer.Cancer drug resistance (Alhambra, Calif.) · 2026Article
- The multifaceted role of E3 ubiquitin ligases in cancer metastasis: mechanisms, targets, and therapeutic implications.Essays in biochemistry · 2025Review
- Early mutational events and clonal dynamics in normal crypts: implications for colorectal tumorigenesis.Human genomics · 2025Review
- Maritoclax Overcomes FBW7 Deficiency-Driven Irinotecan Resistance in Colorectal Cancer by Targeting MCL1.Cancer medicine · 2025Article
- Hypoxia-Induced circPRELID2 Promotes Gastric Cancer Metastasis by Facilitating ZEB2 Translation via PCBP1 O-GlcNAcylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- A set cover algorithm identifies minimal circulating tumour DNA sequencing targets for colorectal cancer detection.Scientific reports · 2025Article
- EMT and cancer stem cells: Drivers of therapy resistance and promising therapeutic targets.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2025Review
- F-box proteins in cancer: from cancer cells to the tumor microenvironment.Cell communication and signaling : CCS · 2025Review
- Role of exosomal non‑coding RNAs in cancer‑associated fibroblast‑mediated therapy resistance (Review).International journal of oncology · 2025Review
- Epithelial-mesenchymal transition in colorectal cancer metastasis and progression: molecular mechanisms and therapeutic strategies.Cell death discovery · 2025Review
- Dualistic role of ZEB1 and ZEB2 in tumor progression.Biology direct · 2025Review
- Understanding pre-metastatic niche formation: implications for colorectal cancer liver metastasis.Journal of translational medicine · 2025Review
- Dynamics of epithelial-mesenchymal plasticity driving cancer drug resistance.Cancer pathogenesis and therapy · 2025Review
- Beyond destruction: emerging roles of the E3 ubiquitin ligase Hakai.Cellular & molecular biology letters · 2025Review
44 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
15 authors at 6 institutions in 4 countries.
Funding
Abstract
Colorectal cancer (CRC) patients develop recurrence after chemotherapy owing to the survival of stem cell-like cells referred to as cancer stem-like cells (CSCs). The origin of CSCs is linked to the epithelial-mesenchymal transition (EMT) process. Currently, it remains poorly understood how EMT programmes enable CSCs residing in the tumour microenvironment to escape the effects of chemotherapy. This study identifies a key molecular pathway that is responsible for the formation of drug-resistant CSC populations. Using a modified yeast-2-hybrid system and 2D gel-based proteomics methods, we show that the E3-ubiquitin ligase FBXW7 directly binds and degrades the EMT-inducing transcription factor ZEB2 in a phosphorylation-dependent manner. Loss of FBXW7 induces an EMT that can be effectively reversed by knockdown of ZEB2. The FBXW7-ZEB2 axis regulates such important cancer cell features, as stemness/dedifferentiation, chemoresistance and cell migration in vitro, ex vivo and in animal models of metastasis. High expression of ZEB2 in cancer tissues defines the reduced ZEB2 expression in the cancer-associated stroma in patients and in murine intestinal organoids, demonstrating a tumour-stromal crosstalk that modulates a niche and EMT activation. Our study thus uncovers a new molecular mechanism, by which the CRC cells display differences in resistance to chemotherapy and metastatic potential.
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Registered trials
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.