ArticleJournal of experimental & clinical cancer research : CR2018
RHBDD1 promotes colorectal cancer metastasis through the Wnt signaling pathway and its downstream target ZEB1.
Article in Journal of experimental & clinical cancer research : CR, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 97 citations in OpenAlex.
- Implication of Epigenetic Alterations of ZEB1 in Colorectal Cancer (CRC) Pathogenesis and Therapy Development.Current issues in molecular biology · 2026Review
- K48-ubiquitin-dependent proteases cut-up post-ER proteins.Nature communications · 2026Article
- Identification of Ferroptosis-Related Prognostic Models and FDFT1 as a Potential Ferroptosis Driver in Colorectal Cancer.Current medicinal chemistry · 2026Article
- Neural influences in colorectal cancer progression and therapeutic strategies.International journal of colorectal disease · 2025Review
- Polyphyllin I Inhibits the Metastasis of Cervical Cancer Through the Regulation of the β-Catenin Signaling Pathway.International journal of molecular sciences · 2025Article
- Loss of the APP regulator RHBDL4 preserves memory in an Alzheimer's disease mouse model.Cell death & disease · 2025Article
- Article
- Regulation of RHBDD1 in the invasion of esophageal cancer cells via ELK3/Wnt/β-catenin signaling pathway.Frontiers in bioengineering and biotechnology · 2025Article
- AnbioRxiv : the preprint server for biology · 2024Article
- Single-cell exome sequencing reveals polyclonal seeding and TRPS1 mutations in colon cancer metastasis.Signal transduction and targeted therapy · 2024Article
- Activity-Based Protein Profiling of RHBDL4 Reveals Proteolysis of the Enzyme and a Distinct Inhibitor Profile.ACS chemical biology · 2024Article
- Proteomic characterization identifies clinically relevant subgroups of soft tissue sarcoma.Nature communications · 2024Article
- Wnt/β-catenin-driven EMT regulation in human cancers.Cellular and molecular life sciences : CMLS · 2024Review
- Review
- Circular RNA RHBDD1 regulates tumorigenicity and ferroptosis in colorectal cancer by mediating the ELAVL1/SCD mRNA interaction.Cancer gene therapy · 2024Article
- MiR-5195-3p functions as a tumor suppressor by targeting RHBDD1 in ovarian cancer.Histology and histopathology · 2023Article
- A novel RIP1-mediated canonical WNT signaling pathway that promotes colorectal cancer metastasis via β -catenin stabilization-induced EMT.Cancer gene therapy · 2023Article
- Exploring the prognostic function of TMB-related prognostic signature in patients with colon cancer.BMC medical genomics · 2023Article
- Article
- The mammalian rhomboid protein RHBDL4 protects against endoplasmic reticulum stress by regulating the morphology and distribution of ER sheets.The Journal of biological chemistry · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
background40-50% of colorectal cancer (CRC) patients develop metastatic disease; the presence of metastasis hinders the effective treatment of cancer through surgery, chemotherapy and radiotherapy, which makes 5-year survival rate extremely low; therefore, studying CRC metastasis is crucial for disease therapy. In the present study, we investigated the role of rhomboid domain containing 1 (RHBDD1) in tumor metastasis of CRC.
methodsThe expression of RHBDD1 was analyzed in 539 colorectal tumor tissues for its correlation with lymphatic metastasis and distal metastasis. Transwell assay in vitro and pleural metastasis analysis in vivo were performed to determine the functions of RHBDD1 during CRC cells metastasis. RNA-seq analysis, TOP/FOP flash reporter assay, western blot and transwell assay were performed to investigate the underlying mechanism for the function of RHBDD1 on Wnt signaling pathway. Bioinformatics analysis was conducted to investigate epithelial-mesenchymal transition (EMT) and stemness in HCT-116 cells. Tissue microarray analysis, Q-PCR and western blot were performed to determine the correlation of RHBDD1 and Zinc Finger E-Box Binding Homeobox 1 (ZEB1).
resultsIn this study, we found that RHBDD1 expression was positively correlated with lymphatic metastasis and distal metastasis in 539 colorectal tumor tissues. RHBDD1 expression can promote CRC cells metastasis in vitro and in vivo. RNA-Seq analysis showed that the Wnt signaling pathway played a key role in this metastatic regulation. RHBDD1 mainly regulated ser552 and ser675 phosphorylation of β-catenin to activate the Wnt signaling pathway. Rescuing ser552 and ser675 phosphorylation of β-catenin resulted in the recovery of signaling pathway activity, migration, and invasion in CRC cells. RHBDD1 promoted EMT and a stem-like phenotype of CRC cells. RHBDD1 regulated the Wnt/β-catenin target gene ZEB1, a potent EMT activator, at the RNA and protein levels. Clinically, RHBDD1 expression was positively correlated with ZEB1 at the protein level in 71 colon tumor tissues.
conclusionsOur findings therefore indicated that RHBDD1 can promote CRC metastasis through the Wnt signaling pathway and ZEB1. RHBDD1 may become a new therapeutic target or clinical biomarker for metastatic CRC.
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