ArticlePLoS biology2021
Noncanonical TGF-β signaling leads to FBXO3-mediated degradation of ΔNp63α promoting breast cancer metastasis and poor clinical prognosis.
Article in PLoS biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 16 papers.
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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.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- TGFβ in malignant canine mammary tumors: relation with angiogenesis, immunologic markers and prognostic role.The veterinary quarterly · 2024Article
- The COP9 signalosome stabilized MALT1 promotes Non-Small Cell Lung Cancer progression through activation of NF-κB pathway.Cell biology and toxicology · 2024Article
- Retraction: Noncanonical TGF-β signaling leads to FBXO3-mediated degradation of ΔNp63α promoting breast cancer metastasis and poor clinical prognosis.PLoS biology · 2024Article
- SEEI: spherical evolution with feedback mechanism for identifying epistatic interactions.BMC genomics · 2024Article
- Complex and variable regulation of ΔNp63 and TAp63 by TGFβ has implications for the dynamics of squamous cell epithelial to mesenchymal transition.Scientific reports · 2024Article
- Article
- A network map of cytoskeleton-associated protein 4 (CKAP4) mediated signaling pathway in cancer.Journal of cell communication and signaling · 2023Article
- The dual role of p63 in cancer.Frontiers in oncology · 2023Review
- The p53 Family Members p63 and p73 Roles in the Metastatic Dissemination: Interactions with microRNAs and TGFβ Pathway.Cancers · 2022Review
- E3 Ubiquitin Ligase FBXO3 Drives Neuroinflammation to Aggravate Cerebral Ischemia/Reperfusion Injury.International journal of molecular sciences · 2022Article
- Distinct interactors define the p63 transcriptional signature in epithelial development or cancer.The Biochemical journal · 2022Article
- The role of long non-coding RNAs in angiogenesis and anti-angiogenic therapy resistance in cancer.Molecular therapy. Nucleic acids · 2022Review
- Article
- Robust Prediction of Prognosis and Immunotherapeutic Response for Clear Cell Renal Cell Carcinoma Through Deep Learning Algorithm.Frontiers in immunology · 2022Article
- TGF-β1 Facilitates TAp63α Protein Lysosomal Degradation to Promote Pancreatic Cancer Cell Migration.Biology · 2021Article
- Diverse Roles of F-BoxProtein3 in Regulation of Various Cellular Functions.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
- Retraction · 2024-06-27Concerns/Issues about Data · Concerns/Issues about Image · Duplication of/in Image · Error in Image · Euphemisms for Duplication · Original Data and/or Images not Provided and/or not Available · Unreliable Data · Unreliable Results and/or Conclusions ·
- Retracted
Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transforming growth factor-β (TGF-β) signaling plays a critical role in promoting epithelial-to-mesenchymal transition (EMT), cell migration, invasion, and tumor metastasis. ΔNp63α, the major isoform of p63 protein expressed in epithelial cells, is a key transcriptional regulator of cell adhesion program and functions as a critical metastasis suppressor. It has been documented that the expression of ΔNp63α is tightly controlled by oncogenic signaling and is frequently reduced in advanced cancers. However, whether TGF-β signaling regulates ΔNp63α expression in promoting metastasis is largely unclear. In this study, we demonstrate that activation of TGF-β signaling leads to stabilization of E3 ubiquitin ligase FBXO3, which, in turn, targets ΔNp63α for proteasomal degradation in a Smad-independent but Erk-dependent manner. Knockdown of FBXO3 or restoration of ΔNp63α expression effectively rescues TGF-β-induced EMT, cell motility, and tumor metastasis in vitro and in vivo. Furthermore, clinical analyses reveal a significant correlation among TGF-β receptor I (TβRI), FBXO3, and p63 protein expression and that high expression of TβRI/FBXO3 and low expression of p63 are associated with poor recurrence-free survival (RFS). Together, these results demonstrate that FBXO3 facilitates ΔNp63α degradation to empower TGF-β signaling in promoting tumor metastasis and that the TβRI-FBXO3-ΔNp63α axis is critically important in breast cancer development and clinical prognosis. This study suggests that FBXO3 may be a potential therapeutic target for advanced breast cancer treatment.
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Registered trials
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