Evidence map›Paper›PMID 35996148›Full record

ArticleJournal of experimental & clinical cancer research : CR2022

GRK3 is a poor prognosticator and serves as a therapeutic target in advanced gastric adenocarcinoma.

Yuan Li, Yibo Fan, Jinbang Xu, Longfei Huo, Ailing W Scott, Jiankang Jin, Boxuan Yang, Shan Shao, Lang Ma, Ying Wang and 12 more

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

Article in Journal of experimental & clinical cancer research : CR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.8field-weighted citation impact, top 31% 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

7 citing papers in PubMed, 9 citations in OpenAlex.

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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

22 authors at 5 institutions in 2 countries.

Yuan Li *Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA.
Yibo Fan *Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA.
Jinbang XuBrown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, McGovern Medical School, The University of Texas Health Science Center, 1825 Pressler St., Houston, TX, 77030, USA.
Longfei HuoDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA.
Ailing W ScottDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA.
Jiankang JinDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA.
Boxuan YangBrown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, McGovern Medical School, The University of Texas Health Science Center, 1825 Pressler St., Houston, TX, 77030, USA.
Shan ShaoDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA.
Lang MaDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA.
Ying WangDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA.
Xiaodan YaoDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA.
Melissa Pool PizziDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA.
Matheus Sewastjanow Da SilvaDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA.
Guoliang ZhangBrown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, McGovern Medical School, The University of Texas Health Science Center, 1825 Pressler St., Houston, TX, 77030, USA.
Lijuan ZhuoBrown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, McGovern Medical School, The University of Texas Health Science Center, 1825 Pressler St., Houston, TX, 77030, USA.
Eun Jeong ChoDivision of Chemical Biology and Medicinal Chemistry, College of Pharmacy, The University of Texas at Austin, Austin, TX, 78712, USA.
Kevin N DalbyDivision of Chemical Biology and Medicinal Chemistry, College of Pharmacy, The University of Texas at Austin, Austin, TX, 78712, USA.
Namita D ShanbhagDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA.
Zhenning WangDepartment of Surgical Oncology and General Surgery, First Hospital of China Medical University, Shenyang, 110001, People's Republic of China. josieon826@sina.cn.
Wenliang LiBrown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, McGovern Medical School, The University of Texas Health Science Center, 1825 Pressler St., Houston, TX, 77030, USA. wenliang.li@uth.tmc.edu.
Shumei SongDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA. ssong@mdanderson.org.ORCID http://orcid.org/0000-0002-8128-6287
Jaffer A AjaniDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA. jajani@mdanderson.org.ORCID http://orcid.org/0000-0001-9946-0629
The University of Texas MD Anderson Cancer Center · USBrown Foundation · USThe University of Texas at Austin · USFirst Hospital of China Medical University · CNFujian Medical University · CN

Funding

Molecular dissecting and targeting YAP1 mediated cancer stemness and immune suppression in advanced gastric adenocarcinomaR01CA269685 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI SONG, SHUMEI · 2022 to 2025
$2.2M
Dissecting and targeting a novel vulnerability in aggressive Rb1 and p53 doubly deficient prostate cancerR01CA270096 · NCI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI Wenliang Li · 2022 to 2026
$1.8M
The Role of Telomere Shortening in MDS-AML Pathogenesis (resubmission)R01CA160433 · NCI · JOHNS HOPKINS UNIVERSITY · PI ARMANIOS, MARY Y · 2012 to 2016
$1.7M
Prediction of Pathologic Complete Response by Gene Expression Profiling in EsophaR01CA138671 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI AJANI, JAFFER A. · 2010 to 2014
$1.5M
Molecular Biomarkers as Classifiers to Individualize Therapy of Esophagus CancerR21CA129906 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI AJANI, JAFFER A. · 2009 to 2010
$367k
NCI NIH HHS CA129906NCI NIH HHS CA138671NCI NIH HHS R01 CA138671NCI NIH HHS R01 CA160433NCI NIH HHS R01 CA269685NCI NIH HHS R01 CA270096NCI NIH HHS R21 CA129906
6 · The paper itself

Abstract

backgroundG protein-coupled receptor (GPCR) is the most targeted protein family by the FDA-approved drugs. GPCR-kinase 3 (GRK3) is critical for GPCR signaling. Our genomic analysis showed that GRK3 expression correlated with poor prognosis of gastric adenocarcinoma (GAC) patients. However, GRK3's functions and clinical utility in GAC progression and metastases are unknown.

methodsWe studied GRK3 expression in normal, primary, and metastatic GAC tissues. We identified a novel GRK3 inhibitor, LD2, through a chemical-library screen. Through genetic and pharmacologic modulations of GRK3, a series of functional and molecular studies were performed in vitro and in vivo. Impact of GRK3 on YAP1 and its targets was determined.

resultsGRK3 was overexpressed in GAC tissues compared to normal and was even higher in peritoneal metastases. Overexpression (OE) of GRK3 was significantly associated with shorter survival. Upregulation of GRK3 in GAC cells increased cell invasion, colony formation, and proportion of ALDH1

conclusionsGRK3, a poor prognosticator for survival, conferred aggressive phenotype. Genetic silencing of GRK3 or its inhibitor LD2 blunted GRK3-conferred malignant attributes, suggesting GRK3 as a novel therapeutic target in advanced GAC.

Indexed as

AdenocarcinomaPeritoneal NeoplasmsStomach NeoplasmsCell Line, TumorCell ProliferationGene Expression Regulation, NeoplasticHumansGastric adenocarcinomaGRK3Hippo/YAP1Peritoneal metastasesPrognosis

Identifiers

PMID35996148
PMCPMC9396876
OpenAlexW4292688627

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.