ArticleInternational journal of molecular sciences2020
TRAP1 Regulates Wnt/β-Catenin Pathway through LRP5/6 Receptors Expression Modulation.
Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 14 citations in OpenAlex.
- Spatial transcriptomics and scRNA-seq: decoding tumor complexity and constructing prognostic models in colorectal cancer.Human genomics · 2025Article
- Tumor necrosis factor receptor-associated protein 1 promotes aerobic glycolysis and cisplatin resistance by regulating the Wnt/β-catenin signaling pathway in lung cancer.Histology and histopathology · 2025Article
- Tumor necrosis factor receptor-associated protein 1 promotes aerobic glycolysis and cisplatin resistance by regulating the Wnt/β-catenin signaling pathway in lung cancer.Histology and histopathology · 2025Article
- Molecular mechanism, diagnosis, and treatment of VACTERL association.Frontiers in pediatrics · 2025Review
- Anorectal malformations.Nature reviews. Disease primers · 2024Review
- The development of cancers research based on mitochondrial heat shock protein 90.Frontiers in oncology · 2023Review
- Jin-Tian-Ge ameliorates ovariectomy-induced bone loss in rats and modulates osteoblastogenesis and osteoclastogenesis in vitro.Chinese medicine · 2022Article
- LRP5 promotes cancer stem cell traits and chemoresistance in colorectal cancer.Journal of cellular and molecular medicine · 2022Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Wnt/β-Catenin signaling is involved in embryonic development, regeneration, and cellular differentiation and is responsible for cancer stemness maintenance. The HSP90 molecular chaperone TRAP1 is upregulated in 60-70% of human colorectal carcinomas (CRCs) and favors stem cells maintenance, modulating the Wnt/β-Catenin pathway and preventing β-Catenin phosphorylation/degradation. The role of TRAP1 in the regulation of Wnt/β-Catenin signaling was further investigated in human CRC cell lines, patient-derived spheroids, and CRC specimens. TRAP1 relevance in the activation of Wnt/β-Catenin signaling was highlighted by a TCF/LEF Cignal Reporter Assay in Wnt-off HEK293T and CRC HCT116 cell lines. Of note, this regulation occurs through the modulation of Wnt ligand receptors LRP5 and LRP6 that are both downregulated in TRAP1-silenced cell lines. However, while LRP5 mRNA is significantly downregulated upon TRAP1 silencing, LRP6 mRNA is unchanged, suggesting independent mechanisms of regulation by TRAP1. Indeed, LRP5 is regulated upon promoter methylation in CRC cell lines and human CRCs, whereas LRP6 is controlled at post-translational level by protein ubiquitination/degradation. Consistently, human CRCs with high TRAP1 expression are characterized by the co-upregulation of active β-Catenin, LRP5 and LRP6. Altogether, these data suggest that Wnt/β-Catenin signaling is modulated at multiple levels by TRAP1.
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