Evidence map›Paper›PMID 36054930›Full record

ArticleNeuro-oncology2023

A distinct pattern of growth and RAC1 signaling in melanoma brain metastasis cells.

Ioana Stejerean-Todoran, Phyllis A Gimotty, Andrea Watters, Patricia Brafford, Clemens Krepler, Tetiana Godok, Haiyin Li, Zuriñe Bonilla Del Rio, Anke Zieseniss, Dörthe M Katschinski and 14 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuro-oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.5field-weighted citation impact, top 38% 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

4 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. 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

24 authors at 6 institutions in 3 countries.

Ioana Stejerean-TodoranDepartment of Cardiovascular Physiology, Molecular Physiology, University Medical Center Göttingen, Göttingen, Germany.
Phyllis A GimottyDepartment of Biostatistics, Informatics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania,USA.
Andrea WattersProgram of Cellular and Molecular Oncogenesis, Melanoma Research Center, The Wistar Institute, Philadelphia, Pennsylvania,USA.
Patricia BraffordProgram of Cellular and Molecular Oncogenesis, Melanoma Research Center, The Wistar Institute, Philadelphia, Pennsylvania,USA.
Clemens KreplerProgram of Cellular and Molecular Oncogenesis, Melanoma Research Center, The Wistar Institute, Philadelphia, Pennsylvania,USA.
Tetiana GodokProgram of Cellular and Molecular Oncogenesis, Melanoma Research Center, The Wistar Institute, Philadelphia, Pennsylvania,USA.
Haiyin LiProgram of Cellular and Molecular Oncogenesis, Melanoma Research Center, The Wistar Institute, Philadelphia, Pennsylvania,USA.
Zuriñe Bonilla Del RioDepartment of Cardiovascular Physiology, Molecular Physiology, University Medical Center Göttingen, Göttingen, Germany.
Anke ZiesenissDepartment of Cardiovascular Physiology, University Medical Center Göttingen, Göttingen, Germany.
Dörthe M KatschinskiDepartment of Cardiovascular Physiology, University Medical Center Göttingen, Göttingen, Germany.
Sinem M SertelDepartment of Neuro- and Sensory Physiology, University Medical Center Göttingen, Göttingen, Germany.
Silvio O RizzoliDepartment of Neuro- and Sensory Physiology, University Medical Center Göttingen, Göttingen, Germany.
Bradley GarmanDepartment of Medicine, Division of Translational Medicine and Human Genetics; Abramson Cancer Center; University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania,USA.
Katherine L NathansonDepartment of Medicine, Division of Translational Medicine and Human Genetics; Abramson Cancer Center; University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania,USA.
Xiaowei XuDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania,USA.
Qing ChenImmunology Microenvironment and Metastasis, The Wistar Institute, Philadelphia, Pennsylvania,USA.
Jack H OswaldImmunology Microenvironment and Metastasis, The Wistar Institute, Philadelphia, Pennsylvania,USA.
Michal LotemSharett Institute of Oncology, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
Gordon B MillsDepartment of Melanoma Medical Oncology, MD Anderson Cancer Center, University of Texas, Houston, Texas,USA.
Michael A DaviesDepartment of Melanoma Medical Oncology, MD Anderson Cancer Center, University of Texas, Houston, Texas,USA.
Michael P SchönDepartment of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Göttingen, Germany.
Ivan BogeskiDepartment of Cardiovascular Physiology, Molecular Physiology, University Medical Center Göttingen, Göttingen, Germany.
Meenhard HerlynProgram of Cellular and Molecular Oncogenesis, Melanoma Research Center, The Wistar Institute, Philadelphia, Pennsylvania,USA.
Adina VulturDepartment of Cardiovascular Physiology, Molecular Physiology, University Medical Center Göttingen, Göttingen, Germany.ORCID 0000-0003-0068-9496
The Wistar Institute · USUniversitätsmedizin Göttingen · DEAbramson Cancer CenterThe University of Texas MD Anderson Cancer Center · USUniversity of Pennsylvania · USHadassah Medical Center · IL

Funding

Tumor Microenvironment and MetastasisP30CA010815 · NCI · WISTAR INSTITUTE · PI Luis J Montaner · 1985 to 2026
$75.9M
Targeting the MAP and PI3 Kinase Pathways in MelanomaP01CA114046 · NCI · WISTAR INSTITUTE · PI MURPHY, MAUREEN E. · 2008 to 2023
$37.1M
TUMOR DEVELOPMENT AND PROGRESSION IN HUMAN MELANOCYTESP01CA025874 · NCI · WISTAR INSTITUTE · PI MARMORSTEIN, RONEN · 1985 to 2015
$19.0M
The University of Texas MD Anderson Cancer Center SPORE in MelanomaP50CA221703 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DAVIES, MICHAEL · 2019 to 2023
$10.3M
METASTATIS: BIOLOGICAL PHENOTYPE AND MODELS FOR THERAPYR01CA047159 · NCI · WISTAR INSTITUTE · PI HERLYN, MEENHARD F · 1989 to 2015
$3.9M
Understanding PPARgamma signaling in melanoma brain metastasisR01CA241490 · NCI · WISTAR INSTITUTE · PI CHEN, QING · 2020 to 2024
$2.0M
Functional Proteomics by Reverse Phase Protein Array in CancerR50CA221675 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI LU, YILING · 2017 to 2021
$726k
NCI NIH HHS P01 CA025874NCI NIH HHS P01 CA114046NCI NIH HHS P30 CA010815NCI NIH HHS P50 CA221703NCI NIH HHS R01 CA047159NCI NIH HHS R01 CA241490NCI NIH HHS R50 CA221675
6 · The paper itself

Abstract

backgroundMelanoma, the deadliest of skin cancers, has a high propensity to form brain metastases that are associated with a markedly worsened prognosis. In spite of recent therapeutic advances, melanoma brain lesions remain a clinical challenge, biomarkers predicting brain dissemination are not clear and differences with other metastatic sites are poorly understood.

methodsWe examined a genetically diverse panel of human-derived melanoma brain metastasis (MBM) and extracranial cell lines using targeted sequencing, a Reverse Phase Protein Array, protein expression analyses, and functional studies in vitro and in vivo.

resultsBrain-specific genetic alterations were not detected; however, MBM cells in vitro displayed lower proliferation rates and MBM-specific protein expression patterns associated with proliferation, DNA damage, adhesion, and migration. MBM lines displayed higher levels of RAC1 expression, involving a distinct RAC1-PAK1-JNK1 signaling network. RAC1 knockdown or treatment with small molecule inhibitors contributed to a less aggressive MBM phenotype in vitro, while RAC1 knockdown in vivo led to reduced tumor volumes and delayed tumor appearance. Proliferation, adhesion, and migration were higher in MBM vs nonMBM lines in the presence of insulin or brain-derived factors and were affected by RAC1 levels.

conclusionsOur findings indicate that despite their genetic variability, MBM engage specific molecular processes such as RAC1 signaling to adapt to the brain microenvironment and this can be used for the molecular characterization and treatment of brain metastases.

Indexed as

Brain NeoplasmsMelanomaSkin NeoplasmsBiomarkersHumansPrognosisrac1 GTP-Binding ProteinTumor MicroenvironmentBiomarkersrac1 GTP-Binding ProteinRAC1 protein, humanbrainmelanomametastasismicroenvironmentRAC1

Identifiers

PMID36054930
PMCPMC10076948
OpenAlexW4294335609

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.