Evidence map›Paper›PMID 41910118›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

Delivery of Pleckstrin-Homology Domains Suppresses PI3K/Akt Signaling and Breast Cancer Metastasis.

Matthew Eason, Anindya Sen, Suhan Cho, Se Jong Lee, Keyata Thompson, Md Musavvir Mahmud, Poornima Dubey, Talia Guardia, Anthony Kim, Stuart Martin and 3 more

Erratum issuedAbstract read
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In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. 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 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Matthew EasonDepartment of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Anindya SenDepartment of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland, USA.
Suhan ChoDepartment of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Se Jong LeeDepartment of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland, USA.
Keyata ThompsonMarlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, Maryland, USA.
Md Musavvir MahmudMarlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, Maryland, USA.
Poornima DubeyMarlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, Maryland, USA.
Talia GuardiaDepartment of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Anthony KimMarlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, Maryland, USA.
Stuart MartinMarlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, Maryland, USA.
Nathan WrightDepartment of Chemistry and Biochemistry, James Madison University, Harrisonburg, Virginia, USA.
Konstantinos KonstantopoulosDepartment of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland, USA.
Aikaterini Kontrogianni-KonstantopoulosDepartment of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland, USA.ORCID https://orcid.org/0000-0003-3948-1959

Funding

Training Grant in Cancer BiologyT32CA154274 · NCI · UNIVERSITY OF MARYLAND BALTIMORE · PI Toni M Antalis, CURT I CIVIN · 2011 to 2026
$6.8M
Tubulin microtentacles in detached mammary epithelial cellsR01CA124704 · NCI · UNIVERSITY OF MARYLAND BALTIMORE · PI MARTIN, STUART S · 2007 to 2025
$5.7M
Development of high throughput screening technologies in breast cancerR01CA183804 · NCI · JOHNS HOPKINS UNIVERSITY · PI KONSTANTOPOULOS, KONSTANTINOS, KONTROGIANNI-KONSTANTOPOULOS, AIKATERINI · 2015 to 2019
$3.5M
The interplay of ion transporters and cytoskeleton in breast cancer migration and metastasisR01CA254193 · NCI · JOHNS HOPKINS UNIVERSITY · PI KONSTANTOPOULOS, KONSTANTINOS, MARTIN, STUART S · 2021 to 2025
$2.7M
The interplay of extracellular fluid viscosity, stiffness and confinement in regulating cell responsesR35GM156305 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI Konstantinos Konstantopoulos · 2025 to 2026
$959k
Obscurin-Deficient Breast Epithelia Generate Secreted Factors that Prime Lung Vascular Smooth Muscle Cell Pre-metastatic Microenvironment FormationF30CA278384 · NCI · UNIVERSITY OF MARYLAND BALTIMORE · PI EASON, MATTHEW KENT · 2023 to 2025
$147k
National Science Foundation MCB2024182NCI NIH HHS CA254193NCI NIH HHS F30 CA278384NCI NIH HHS R01 CA124704NCI NIH HHS R01 CA183804NCI NIH HHS R01 CA254193NCI NIH HHS T32 CA154274NIGMS NIH HHS GM148809NIGMS NIH HHS R35 GM156305NIH/NCI 5F30CA278384NIH/NCI CA124704NIH/NCI CA183804NIH/NIGMS R35GM156305
6 · The paper itself

Abstract

Current cancer therapies inhibit tumor growth but fail to target metastatic dissemination. Obscurin (720-870 kDa), a giant signaling protein localizing to the breast epithelial cell membrane, is a metastasis suppressor commonly lost in breast cancer. Obscurin loss upregulates the oncogenic PI3K/Akt axis. While restoring obscurin expression is crucial from a translational standpoint, it poses major challenges due to its immense size. Herein, we overcome this hurdle by delivering a mini-obscurin-comprising the obscurin-pleckstrin homology (PH) domain, which is ∼50-times smaller than the full-length protein-into aggressive breast cancer cells via adenovirus and lipid nanoparticles. Mechanistically, the obscurin-PH-domain interacts with the PI3K-p85 regulatory subunit. Membrane-targeted obscurin-PH sequesters p85, suppressing PI3K/Akt activity. p85-sequestration eliminates filopodia, hampering migration and adhesion to pre-metastatic niche extracellular matrix substrates. This intervention further eradicates invadopodia and reduces matrix metalloproteinase expression, blocking invasion, dissemination, and metastasis. We recapitulate this phenotype using the structurally homologous kalirin and PLCγ1 PH-domains and ultimately uncover a family of nine PH-domains that may act as PI3K inhibitors, unified by the "p85 inhibitory metastasis suppressor" (PIMS) motif, mediating this effect. This work engineers a first-in-class group of non-chemical PI3K inhibitors, uniquely targeting the PI3K-p85 subunit, galvanizing novel gene therapies for treating metastatic breast cancer.

Indexed as

Breast NeoplasmsPhosphatidylinositol 3-KinasesPleckstrin Homology DomainsProto-Oncogene Proteins c-aktRho Guanine Nucleotide Exchange FactorsAnimalsCell Line, TumorCell MovementFemaleHumansMiceNeoplasm MetastasisSignal TransductionPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktRho Guanine Nucleotide Exchange Factorsbreast cancermetastasis suppressorsobscurinPI3K/Akt signalingPI3K inhibitorspleckstrin homology domains

Identifiers

PMID41910118
PMCPMC13248768

What OpenQuestion holds

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Registered trials

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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.