ArticleCell death discovery2025
HUWE1 loss promotes stemness and drug resistance in CRC with dysregulated β-catenin destruction complex.
Article in Cell death discovery, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
1 citing paper in PubMed.
- Mechanisms and advances of drug resistance in colorectal cancer: A systematic overview of multi-layered regulatory networks.Translational oncology · 2026Review
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Cancer stem cells (CSCs) are a key driver of tumor initiation, progression, and drug resistance in colorectal cancer (CRC). The Wnt/β-catenin signaling pathway, which is hyperactivated in nearly all CRC cases, plays a crucial role in CSC-related processes such as proliferation, epithelial-mesenchymal transition (EMT), and metastasis. In this study, we demonstrate that HUWE1 plays a critical regulator of Wnt/β-catenin signaling, similar to the β-catenin destruction complex. Under conditions of β-catenin destruction complex inactivation, most HUWE1 directly interacts with and ubiquitinates β-catenin. Conversely, when the destruction complex is active, HUWE1 targets upstream proteins for ubiquitination, thereby regulating Wnt/β-catenin signaling. This highlights HUWE1 as a pivotal regulator of Wnt/β-catenin signaling, particularly in CRC cases characterized by frequent APC mutations. Our findings further show that HUWE1 loss in CRC cells stabilizes β-catenin, enhancing CSC traits and promoting EMT. Additionally, HUWE1 depletion leads to excessive mitochondrial biogenesis, which contributes to drug resistance by supplying significant ATP levels to ATP-binding cassette (ABC) transporters. In conclusion, this study uncovers a previously unrecognized role of HUWE1 in regulating Wnt/β-catenin signaling and its impact on CRC. These insights may aid in identifying colorectal CSCs and developing targeted therapeutic strategies.
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Registered trials
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