Evidence map›Paper›PMID 37500798›Full record

ArticleOncogene2023

Activation of NFAT by HGF and IGF-1 via ARF6 and its effector ASAP1 promotes uveal melanoma metastasis.

Jackson R Richards, Donghan Shin, Rob Pryor, Lise K Sorensen, Zhonglou Sun, Won Mi So, Garam Park, Roger Wolff, Amanda Truong, Martin McMahon and 5 more

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in Oncogene, 2023. 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 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
2.5field-weighted citation impact, top 11% 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

10 citing papers in PubMed, 9 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 4 institutions in 1 country.

Jackson R RichardsDepartment of Oncological Sciences, School of Medicine, University of Utah, 2000 Circle of Hope Drive, Salt Lake City, UT, 84112, USA.
Donghan ShinDepartment of Medicine, Program in Molecular Medicine, University of Utah, 15 North 2030 East, Salt Lake City, UT, 84112, USA.
Rob PryorDepartment of Medicine, Program in Molecular Medicine, University of Utah, 15 North 2030 East, Salt Lake City, UT, 84112, USA.
Lise K SorensenDepartment of Medicine, Program in Molecular Medicine, University of Utah, 15 North 2030 East, Salt Lake City, UT, 84112, USA.
Zhonglou SunDepartment of Medicine, Program in Molecular Medicine, University of Utah, 15 North 2030 East, Salt Lake City, UT, 84112, USA.
Won Mi SoDepartment of Ophthalmology & Visual Sciences, Truhlsen Eye Institute, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Garam ParkDepartment of Ophthalmology & Visual Sciences, Truhlsen Eye Institute, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Roger WolffDepartment of Pathology, University of Utah, 15 North Medical Drive East, Salt Lake City, UT, 84112, USA.
Amanda TruongDepartment of Oncological Sciences, School of Medicine, University of Utah, 2000 Circle of Hope Drive, Salt Lake City, UT, 84112, USA.
Martin McMahonDepartment of Oncological Sciences, School of Medicine, University of Utah, 2000 Circle of Hope Drive, Salt Lake City, UT, 84112, USA.ORCID http://orcid.org/0000-0003-2812-1042
Allie H GrossmannDepartment of Pathology, University of Utah, 15 North Medical Drive East, Salt Lake City, UT, 84112, USA.
J William HarbourDepartment of Ophthalmology, Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, 75390, USA.ORCID http://orcid.org/0000-0002-1104-9809
Weiquan ZhuDepartment of Medicine, Program in Molecular Medicine, University of Utah, 15 North 2030 East, Salt Lake City, UT, 84112, USA.
Shannon J Odelberg *Department of Medicine, Program in Molecular Medicine, University of Utah, 15 North 2030 East, Salt Lake City, UT, 84112, USA. sodelber@genetics.utah.edu.ORCID http://orcid.org/0000-0001-5935-0468
Jae Hyuk Yoo *Department of Ophthalmology & Visual Sciences, Truhlsen Eye Institute, University of Nebraska Medical Center, Omaha, NE, 68198, USA. jyoo@unmc.edu.ORCID http://orcid.org/0000-0001-9359-8109
University of Utah · USUniversity of Nebraska Medical Center · USSouthwestern Medical CenterUniversity of Iowa · US

Funding

UTAH REGIONAL CANCER CENTERP30CA042014 · NCI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Jared P Rutter · 1986 to 2026
$72.6M
Target Validation CoreP20GM121316 · NIGMS · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI Robert E. Lewis · 2018 to 2026
$23.5M
Identifying a nodal point for G alpha q signaling in eye diseaseR01CA202778 · NCI · UNIVERSITY OF UTAH · PI ODELBERG, SHANNON J · 2016 to 2020
$1.7M
ARF6 function in cancers driven by RAS hyperactivationR00CA230312 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI YOO, JAE HYUK · 2021 to 2023
$742k
Non-canonical WNT signaling in the invasion and metastasis of uveal melanomaF30CA217184 · NCI · UNIVERSITY OF UTAH · PI RICHARDS, JACKSON ROYAL · 2017 to 2021
$206k
Defining the role of aberrant signal pathway activation in melanoma on the immune microenvironmentF30CA235964 · NCI · UNIVERSITY OF UTAH · PI TRUONG, AMANDA · 2019 to 2021
$136k
NCI NIH HHS F30 CA217184NCI NIH HHS F30 CA235964NCI NIH HHS P30 CA042014NCI NIH HHS R00 CA230312NCI NIH HHS R01 CA202778NIGMS NIH HHS P20 GM121316
6 · The paper itself

Abstract

Preventing or effectively treating metastatic uveal melanoma (UM) is critical because it occurs in about half of patients and confers a very poor prognosis. There is emerging evidence that hepatocyte growth factor (HGF) and insulin-like growth factor 1 (IGF-1) promote metastasis and contribute to the striking metastatic hepatotropism observed in UM metastasis. However, the molecular mechanisms by which HGF and IGF-1 promote UM liver metastasis have not been elucidated. ASAP1, which acts as an effector for the small GTPase ARF6, is highly expressed in the subset of uveal melanomas most likely to metastasize. Here, we found that HGF and IGF-1 hyperactivate ARF6, leading to its interaction with ASAP1, which then acts as an effector to induce nuclear localization and transcriptional activity of NFAT1. Inhibition of any component of this pathway impairs cellular invasiveness. Additionally, knocking down ASAP1 or inhibiting NFAT signaling reduces metastasis in a xenograft mouse model of UM. The discovery of this signaling pathway represents not only an advancement in our understanding of the biology of uveal melanoma metastasis but also identifies a novel pathway that could be targeted to treat or prevent metastatic uveal melanoma.

Indexed as

MelanomaUveal NeoplasmsAdaptor Proteins, Signal TransducingAnimalsDisease Models, AnimalHepatocyte Growth FactorHumansInsulin-Like Growth Factor IMiceUveal MelanomaAdaptor Proteins, Signal TransducingASAP1 protein, humanHepatocyte Growth FactorHGF protein, humanInsulin-Like Growth Factor I

Identifiers

PMID37500798
PMCPMC11008337
OpenAlexW4385304119

What Socratic holds

Textmetadata
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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.