ArticleOncotarget2016
APPL proteins promote TGFβ-induced nuclear transport of the TGFβ type I receptor intracellular domain.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- Targeting oncogenic TβRI signaling inhibits androgen-independent prostate cancer growth and metastasis.Signal transduction and targeted therapy · 2026Article
- Pathogenesis-Guided Biomarker Assessment: A Shift in Prostate Cancer Diagnostics.International journal of molecular sciences · 2025Review
- Article
- Novel Histopathological Biomarkers in Prostate Cancer: Implications and Perspectives.Biomedicines · 2023Review
- Involvement of adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1 in diallyl trisulfide-induced cytotoxicity in hepatocellular carcinoma cells.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2022Article
- The ubiquitin-ligase TRAF6 and TGFβ type I receptor form a complex with Aurora kinase B contributing to mitotic progression and cytokinesis in cancer cells.EBioMedicine · 2022Article
- Review
- CAM-Delam: an in vivo approach to visualize and quantify the delamination and invasion capacity of human cancer cells.Scientific reports · 2020Article
- Interactions between TGF-β type I receptor and hypoxia-inducible factor-α mediates a synergistic crosstalk leading to poor prognosis for patients with clear cell renal cell carcinoma.Cell cycle (Georgetown, Tex.) · 2019Article
- TGFβ activates PI3K-AKT signalingOncotarget · 2017Article
- APPL1 is a multifunctional endosomal signaling adaptor protein.Biochemical Society transactions · 2017Review
- Synergistic immunologic targets for the treatment of prostate cancer.Experimental biology and medicine (Maywood, N.J.) · 2016Review
- APPL1-Mediating Leptin Signaling Contributes to Proliferation and Migration of Cancer Cells.PloS one · 2016Article
- Identification of progression markers for prostate cancer.Cell cycle (Georgetown, Tex.)Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The multifunctional cytokine transforming growth factor-β (TGFβ) is produced by several types of cancers, including prostate cancer, and promote tumour progression in autocrine and paracrine manners. In response to ligand binding, the TGFβ type I receptor (TβRI) activates Smad and non-Smad signalling pathways. The ubiquitin-ligase tumour necrosis factor receptor-associated factor 6 (TRAF6) was recently linked to regulate intramembrane proteolytic cleavage of the TβRI in cancer cells. Subsequently, the intracellular domain (ICD) of TβRI enters in an unknown manner into the nucleus, where it promotes the transcription of pro-invasive genes, such as MMP2 and MMP9. Here we show that the endocytic adaptor molecules APPL1 and APPL2 are required for TGFβ-induced nuclear translocation of TβRI-ICD and for cancer cell invasiveness of human prostate and breast cancer cell lines. Moreover, APPL proteins were found to be expressed at high levels in aggressive prostate cancer tissues, and to be associated with TβRI in a TRAF6-dependent manner. Our results suggest that the APPL-TβRI complex promotes prostate tumour progression, and may serve as a prognostic marker.
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Registered trials
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