ArticleOncotarget2016
Giant obscurins regulate the PI3K cascade in breast epithelial cells via direct binding to the PI3K/p85 regulatory subunit.
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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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- Delivery of Pleckstrin-Homology Domains Suppresses PI3K/Akt Signaling and Breast Cancer Metastasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Obscurin a localizes near the cell membrane to modulate stress fiber dynamics and cell migration.The Journal of biological chemistry · 2026Article
- Obscurin deficiency leads to compensated dilated cardiomyopathy and increased arrhythmias.The Journal of general physiology · 2025Article
- Novel compound heterozygous OBSCN variants in Chinese children with congenital pulmonary airway malformation.Italian journal of pediatrics · 2025Article
- Essential role of obscurin kinase-1 in cardiomyocyte coupling via N-cadherin phosphorylation.JCI insight · 2024Article
- Article
- Obscurin: A multitasking giant in the fight against cancer.Biochimica et biophysica acta. Reviews on cancer · 2021Review
- Proteomic Analysis of Myocardia Containing the Obscurin R4344Q Mutation Linked to Hypertrophic Cardiomyopathy.Frontiers in physiology · 2020Article
- Article
- Unraveling obscurins in heart disease.Pflugers Archiv : European journal of physiology · 2019Review
- Thick Filament Protein Network, Functions, and Disease Association.Comprehensive Physiology · 2018Review
- Article
- Loss of giant obscurins alters breast epithelial cell mechanosensing of matrix stiffness.Oncotarget · 2017Article
- Obscure functions: the location-function relationship of obscurins.Biophysical reviews · 2017Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Obscurins are a family of giant cytoskeletal proteins, originally identified in striated muscles where they have structural and regulatory roles. We recently showed that obscurins are abundantly expressed in normal breast epithelial cells where they play tumor and metastasis suppressing roles, but are nearly lost from advanced stage breast cancer biopsies. Consistent with this, loss of giant obscurins from breast epithelial cells results in enhanced survival and growth, epithelial to mesenchymal transition (EMT), and increased cell migration and invasion in vitro and in vivo. In the current study, we demonstrate that loss of giant obscurins from breast epithelial cells is associated with significantly increased phosphorylation and subsequent activation of the PI3K signaling cascade, including activation of AKT, a key regulator of tumorigenesis and metastasis. Pharmacological and molecular inhibition of the PI3K pathway in obscurin-depleted breast epithelial cells results in reversal of EMT, (re)formation of cell-cell junctions, diminished mammosphere formation, and decreased cell migration and invasion. Co-immunoprecipitation, pull-down, and surface plasmon resonance assays revealed that obscurins are in a complex with the PI3K/p85 regulatory subunit, and that their association is direct and mediated by the obscurin-PH domain and the PI3K/p85-SH3 domain with a KD of ~50 nM. We therefore postulate that giant obscurins act upstream of the PI3K cascade in normal breast epithelial cells, regulating its activation through binding to the PI3K/p85 regulatory subunit.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.