ArticleMolecular therapy : the journal of the American Society of Gene Therapy2015
Exosome-mediated delivery of the intrinsic C-terminus domain of PTEN protects it from proteasomal degradation and ablates tumorigenesis.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2015. 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 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
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- Harnessing exosomes as a platform for drug delivery in breast cancer: A systematic review forMolecular therapy. Oncology · 2024Review
- Carbon Nanotube-Mediated Delivery of PTEN Variants: In Vitro Antitumor Activity in Breast Cancer Cells.Molecules (Basel, Switzerland) · 2024Article
- HighBrain sciences · 2023Article
- Chaperone-assisted E3 ligase CHIP: A double agent in cancer.Genes & diseases · 2022Review
- Cancer associated-fibroblast-derived exosomes in cancer progression.Molecular cancer · 2021Review
- E3 ligase-inactivation rewires CBL interactome to elicit oncogenesis by hijacking RTK-CBL-CIN85 axis.Oncogene · 2021Article
- Regulation of exosome production and cargo sorting.International journal of biological sciences · 2021Review
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- miR-137: A Novel Therapeutic Target for Human Glioma.Molecular therapy. Nucleic acids · 2020Review
- DELTEX2 C-terminal domain recognizes and recruits ADP-ribosylated proteins for ubiquitination.Science advances · 2020Article
- Promyelocytic Leukemia (PML) gene regulation: implication towards curbing oncogenesis.Cell death & disease · 2019Article
- RNA helicase p68 deploys β-catenin in regulating RelA/p65 gene expression: implications in colon cancer.Journal of experimental & clinical cancer research : CR · 2019Article
- Post-translational add-ons mark the path in exosomal protein sorting.Cellular and molecular life sciences : CMLS · 2018Review
- Roles of Extracellular Vesicles in Metastatic Breast Cancer.Breast cancer : basic and clinical research · 2018Review
- A General Strategy for Discovery of Inhibitors and Activators of RING and U-box E3 Ligases with Ubiquitin Variants.Molecular cell · 2017Article
- Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PTEN mutation is a frequent feature across a plethora of human cancers, the hot-spot being its C-terminus (PTEN-CT) regulatory domain resulting in a much diminished protein expression. In this study, the presence of C-terminus mutations was confirmed through sequencing of different human tumor samples. The kinase CKII-mediated phosphorylation of PTEN at these sites makes it a loopy structure competing with the E3 ligases for binding to its lipid anchoring C2 domain. Accordingly, it was found that PTEN-CT expressing stable cell lines could inhibit tumorigenesis in syngenic breast tumor models. Therefore, we designed a novel exosome-mediated delivery of the intrinsic PTEN domain, PTEN-CT into different cancer cells and observed reduced proliferation, migration, and colony forming ability. The delivery of exosome containing PTEN-CT to breast tumor mice model was found to result in significant regression in tumor size with the tumor sections showing increased apoptosis. Here, we also report for the first time an active PTEN when its C2 domain is bound by PTEN-CT, probably rendering its anti-tumorigenic activities through the protein phosphatase activity. Therefore, therapeutic interventions that focus on PTEN E3 ligase inhibition through exosome-mediated PTEN-CT delivery can be a probable route in treating cancers with low PTEN expression.
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