Evidence map›Paper›PMID 36044842›Full record

ArticleCell reports2022

ABL kinases regulate translation in HER2+ cells through Y-box-binding protein 1 to facilitate colonization of the brain.

Courtney M McKernan, Aaditya Khatri, Molly Hannigan, Jessica Child, Qiang Chen, Benjamin Mayro, David Snyder, Christopher V Nicchitta, Ann Marie Pendergast

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.6field-weighted citation impact, top 36% of its field
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

6 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. YB-1 activating cascades as potential targets in KRAS-mutated tumors.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2023
    Review
  5. Article
  6. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

Courtney M McKernanDepartment of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710, USA.
Aaditya KhatriDepartment of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
Molly HanniganDepartment of Cell Biology, Duke University School of Medicine, Durham, NC 27710, USA.
Jessica ChildDepartment of Cell Biology, Duke University School of Medicine, Durham, NC 27710, USA.
Qiang ChenDepartment of Cell Biology, Duke University School of Medicine, Durham, NC 27710, USA.
Benjamin MayroDepartment of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710, USA.
David SnyderDepartment of Surgery, Duke University School of Medicine, Durham, NC 27710, USA.
Christopher V NicchittaDepartment of Cell Biology, Duke University School of Medicine, Durham, NC 27710, USA.
Ann Marie PendergastDepartment of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710, USA. Electronic address: ann.pendergast@duke.edu.
Duke University · US

Funding

Women's Cancer Research ProgramP30CA014236 · NCI · DUKE UNIVERSITY · PI Laura Fish · 1985 to 2026
$174.8M
Medical Scientist Training Program Training GrantT32GM145449 · NIGMS · DUKE UNIVERSITY · PI Christopher D Kontos · 2022 to 2026
$6.6M
Research Supplements to Promote Diversity in Health-Related ResearchR35GM139480 · NIGMS · DUKE UNIVERSITY · PI Christopher V. Nicchitta · 2021 to 2026
$4.1M
Stimulating Access to Research in Residency (StARR) - NHLBIR38HL143612 · NHLBI · DUKE UNIVERSITY · PI Mai ElMallah, David H. Harpole · 2018 to 2026
$2.6M
mRNA Localization in Organelle BiogenesisR01GM101533 · NIGMS · DUKE UNIVERSITY · PI NICCHITTA, CHRISTOPHER V. · 2012 to 2020
$2.4M
Mechanisms of Translational Compartmentalization in Eukaryotic CellsR01GM118630 · NIGMS · DUKE UNIVERSITY · PI NICCHITTA, CHRISTOPHER V. · 2017 to 2020
$1.5M
The Role of Abl Kinase Signaling in HER2+ Breast Cancer Brain MetastasisF31CA224952 · NCI · DUKE UNIVERSITY · PI MCKERNAN, COURTNEY MICHELLE · 2018 to 2020
$118k
Understanding the impact that tumor representative oxygen tension has on phosphotyrosine-dependent signaling networks in solid tumorsF99CA264162 · NCI · DUKE UNIVERSITY · PI MAYRO, BENJAMIN JACOB · 2021 to 2022
$78k
ABL kinases promote lung cancer brain metastasis through regulation of transcriptional networksF31CA243293 · NCI · DUKE UNIVERSITY · PI MAYRO, BENJAMIN JACOB · 2020 to 2020
$37k
NCI NIH HHS F31 CA224952NCI NIH HHS F31 CA243293NCI NIH HHS F99 CA264162NCI NIH HHS P30 CA014236NHLBI NIH HHS R38 HL143612NIGMS NIH HHS R01 GM101533NIGMS NIH HHS R01 GM118630NIGMS NIH HHS R35 GM139480NIGMS NIH HHS T32 GM145449
6 · The paper itself

Abstract

Patients with human epidermal growth factor receptor 2-positive (HER2+/ERBB2) breast cancer often present with brain metastasis. HER2-targeted therapies have not been successful to treat brain metastases in part due to poor blood-brain barrier (BBB) penetrance and emergence of resistance. Here, we report that Abelson (ABL) kinase allosteric inhibitors improve overall survival and impair HER2+ brain metastatic outgrowth in vivo. Mechanistically, ABL kinases phosphorylate the RNA-binding protein Y-box-binding protein 1 (YB-1). ABL kinase inhibition disrupts binding of YB-1 to the ERBB2 mRNA and impairs translation, leading to a profound decrease in HER2 protein levels. ABL-dependent tyrosine phosphorylation of YB-1 promotes HER2 translation. Notably, loss of YB-1 inhibits brain metastatic outgrowth and impairs expression of a subset of ABL-dependent brain metastatic targets. These data support a role for ABL kinases in the translational regulation of brain metastatic targets through YB-1 and offer a therapeutic target for HER2+ brain metastasis patients.

Indexed as

Brain NeoplasmsBreast NeoplasmsProto-Oncogene Proteins c-ablY-Box-Binding Protein 1BrainCell Line, TumorErb-b2 Receptor Tyrosine KinasesFemaleHumansERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesProto-Oncogene Proteins c-ablY-Box-Binding Protein 1ABL kinasebrain metastasisbreast cancerCP: CancerCP: Molecular biologyHER2mRNA translationRNA-binding proteinY-box-binding protein 1

Identifiers

PMID36044842
PMCPMC9472557
OpenAlexW4293574497

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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 Socratic graph.