Evidence map›Paper›PMID 30456298›Full record

ArticleNPJ breast cancer2018

mTORC1 is a key mediator of RON-dependent breast cancer metastasis with therapeutic potential.

Najme Faham, Ling Zhao, Alana L Welm

Open access · goldAbstract read
In one paragraph

Article in NPJ breast cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.3field-weighted citation impact, top 19% 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

14 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
  2. A network map of macrophage-stimulating protein (MSP) signaling.Journal of cell communication and signaling · 2023
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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

3 authors at 2 institutions in 1 country.

Najme FahamDepartment of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT USA.
Ling ZhaoDepartment of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT USA.
Alana L WelmDepartment of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT USA.
Huntsman Cancer Institute · USUniversity of Utah · US

Funding

UTAH REGIONAL CANCER CENTERP30CA042014 · NCI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Jared P Rutter · 1986 to 2026
$72.6M
Short-form Ron Kinase in Tumor Progression and MetastasisR01CA166422 · NCI · UNIVERSITY OF UTAH · PI WELM, ALANA L · 2012 to 2017
$2.0M
NCI NIH HHS P30 CA042014NCI NIH HHS R01 CA166422
6 · The paper itself

Abstract

Metastasis is the biggest challenge in treating breast cancer, and it kills >40,000 breast cancer patients annually in the US. Aberrant expression of the RON receptor tyrosine kinase in breast tumors correlates with poor prognosis and has been shown to promote metastasis. However, the molecular mechanisms that govern how RON promotes metastasis, and how to block it, are still largely unknown. We sought to determine critical effectors of RON using a combination of mutational and pharmacologic strategies. High-throughput proteomic analysis of breast cancer cells upon activation of RON showed robust phosphorylation of ribosomal protein S6. Further analysis revealed that RON strongly signals through mTORC1/p70S6K, which is mediated predominantly by the PI3K pathway. A targeted mutation approach to modulate RON signaling validated the importance of PI3K/mTORC1 pathway for spontaneous metastasis in vivo. Finally, inhibition of mTORC1 with an FDA-approved drug, everolimus, resulted in transient shrinkage of established RON-dependent metastases, and combined blockade of mTORC1 and RON delayed progression. These studies have identified a key downstream mediator of RON-dependent metastasis in breast cancer cells and revealed that inhibition of mTORC1, or combined inhibition of mTORC1 and RON, may be effective for treatment of metastatic breast cancers with elevated expression of RON.

Identifiers

PMID30456298
PMCPMC6226524
OpenAlexW2900266208

What OpenQuestion holds

Textmetadata
LicenceCC BY
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 OpenQuestion graph.