{"doi":"10.18632/oncotarget.27562","title":"Characterization of GRK5 as a novel regulator of rhabdomyosarcoma tumor cell growth and self-renewal","abstract":"// Thao Pham 1 , Kristin Robinson 1 , Terra Vleeshouwer-Neumann 1 , James E. Annis 2 and Eleanor Y. Chen 1 1 Department of Pathology, University of Washington, Seattle, WA, USA 2 Quellos HTS Core, Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA Correspondence to: Eleanor Y. Chen, email: eleanor2@uw.edu Keywords: rhabdomyosarcoma; self-renewal; GRK5, kinase; cell cycle Received: December 05, 2019     Accepted: April 03, 2020     Published: April 21, 2020 ABSTRACT Rhabdomyosarcoma (RMS) is the most common soft-tissue pediatric sarcoma. Clinical outcomes for RMS patients with relapsed or metastatic disease remain poor. Treatment options remain limited, presenting an urgent need for novel therapeutic targets. Using a high-throughput siRNA screen against the human kinome, we identified GRK5, a G-protein receptor kinase, as a novel regulator of RMS tumor cell growth and self-renewal. Through functional assays in vitro and in vivo , we show that GRK5 regulates cell cycle in a kinase-independent manner to promote RMS tumor cell growth. NFAT1 expression is regulated by GRK5 in a kinase independent manner, and loss of NFAT1 phenocopies GRK5 loss-of-function effects on the cell cycle alterations. Self-renewal of tumor propagating cells (TPCs) is thought to give rise to tumor relapse. We show that loss of GRK5 results in a significant reduction of RMS self-renewal capacity in part due to increased cell death. Treatment of human RMS xenografts in mice with CCG-215022, a GRK5-selective inhibitor, results in reduced tumor growth and self-renewal in both major subtypes of RMS. GRK5 represents a novel therapeutic target for the treatment of RMS.","journal":"Oncotarget","year":2020,"id":107218,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9592,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":444352,"name":"Kristin Robinson","orcid":null,"position":1,"is_corresponding":false},{"id":516870,"name":"Terra Vleeshouwer-Neumann","orcid":null,"position":2,"is_corresponding":false},{"id":23617,"name":"James Annis","orcid":null,"position":3,"is_corresponding":false},{"id":516084,"name":"Eleanor Y. Chen","orcid":"0000-0003-4372-7560","position":4,"is_corresponding":false},{"id":452858,"name":"Thao Pham","orcid":"0000-0002-7667-6897","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-18T23:12:34.898963Z","pmid":"32363002","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}