ArticleCancer research2021
Neural Crest-Like Stem Cell Transcriptome Analysis Identifies LPAR1 in Melanoma Progression and Therapy Resistance.
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Article in Cancer research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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21citing papers in PubMed
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Who cites it
21 citing papers in PubMed, 25 citations in OpenAlex.
- A Multistep Immune-Competent Genetically Engineered Mouse Model Reveals Phenotypic Plasticity in Uveal Melanoma.Cancer research · 2026Article
- The neural crest-associated gene ERRFI1 is involved in melanoma progression and resistance toward targeted therapy.Molecular oncology · 2026Article
- Article
- A Melanoma-Specific Gene Network Analysis Identifies MZB1 as a Potential Tumor Promoter.The Journal of investigative dermatology · 2026Article
- Exploring the significance of GNG11, LPAR1, and AGTR1 in early diagnosis and prognosis of cervical cancer: A correlative analysis with clinical characteristics.Pakistan journal of medical sciences · 2025Article
- Cancer Stem Cells in Melanoma: Drivers of Tumor Plasticity and Emerging Therapeutic Strategies.International journal of molecular sciences · 2025Review
- A multi-step immune-competent genetic mouse model reveals phenotypic plasticity in uveal melanoma.bioRxiv : the preprint server for biology · 2025Article
- Machine learning unravels the mysteries of glioma typing and treatment.Biochemistry and biophysics reports · 2025Article
- Generation of New Knock-Out Mouse Strains ofInternational journal of molecular sciences · 2025Article
- The Use of Biologics for Targeting GPCRs in Metastatic Cancers.Biotech (Basel (Switzerland)) · 2025Review
- LPA suppresses HLA-DR expression in human melanoma cells: a potential immune escape mechanism involving LPAR1 and DR6-mediated release of IL-10.Acta pharmacologica Sinica · 2025Article
- miR-383-3p and miR-6951-3p activate cell proliferation through the regulation of genes related to hypertelorism.Frontiers in cell and developmental biology · 2025Article
- DNA Methylation Classes of Stage II and III Primary Melanomas and Their Clinical and Prognostic Significance.JCO precision oncology · 2024Article
- Exploring the Genetic Landscape of Vitiligo in the Pura Raza Español Horse: A Genomic Perspective.Animals : an open access journal from MDPI · 2024Article
- Determinants of resistance and response to melanoma therapy.Nature cancer · 2024Review
- Article
- Immune escape and metastasis mechanisms in melanoma: breaking down the dichotomy.Frontiers in immunology · 2024Review
- The journey from melanocytes to melanoma.Nature reviews. Cancer · 2023Review
- Sorting Transcriptomics Immune Information from Tumor Molecular Features Allows Prediction of Response to Anti-PD1 Therapy in Patients with Advanced Melanoma.International journal of molecular sciences · 2023Article
- Construction and experimental validation of a signature for predicting prognosis and immune infiltration analysis of glioma based on disulfidptosis-related lncRNAs.Frontiers in immunology · 2023Article
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Authors and funding
48 authors at 7 institutions in 1 country.
Jianglan Liu *Molecular and Cellular Oncogenesis Program and Melanoma Research Center, The Wistar Institute, Philadelphia, Pennsylvania.
Vito W Rebecca *Molecular and Cellular Oncogenesis Program and Melanoma Research Center, The Wistar Institute, Philadelphia, Pennsylvania.
Andrew V KossenkovMolecular and Cellular Oncogenesis Program and Melanoma Research Center, The Wistar Institute, Philadelphia, Pennsylvania.
Thomas ConnellyMolecular and Cellular Oncogenesis Program and Melanoma Research Center, The Wistar Institute, Philadelphia, Pennsylvania.
Qin LiuMolecular and Cellular Oncogenesis Program and Melanoma Research Center, The Wistar Institute, Philadelphia, Pennsylvania.ORCID 0000-0001-9964-580X
Alexis GutierrezMolecular and Cellular Oncogenesis Program and Melanoma Research Center, The Wistar Institute, Philadelphia, Pennsylvania.
Min XiaoMolecular and Cellular Oncogenesis Program and Melanoma Research Center, The Wistar Institute, Philadelphia, Pennsylvania.
Ling LiMolecular and Cellular Oncogenesis Program and Melanoma Research Center, The Wistar Institute, Philadelphia, Pennsylvania.
Gao ZhangMolecular and Cellular Oncogenesis Program and Melanoma Research Center, The Wistar Institute, Philadelphia, Pennsylvania.ORCID 0000-0001-8617-8886
Anastasia SamarkinaMolecular and Cellular Oncogenesis Program and Melanoma Research Center, The Wistar Institute, Philadelphia, Pennsylvania.
Delaine ZayasbazanMolecular and Cellular Oncogenesis Program and Melanoma Research Center, The Wistar Institute, Philadelphia, Pennsylvania.
Jie ZhangDepartment of Computer Science, New Jersey Institute of Technology, Newark, New Jersey.
Chaoran ChengDepartment of Computer Science, New Jersey Institute of Technology, Newark, New Jersey.
Zhi WeiDepartment of Computer Science, New Jersey Institute of Technology, Newark, New Jersey.ORCID 0000-0001-6059-4267
Gretchen M AliceaMolecular and Cellular Oncogenesis Program and Melanoma Research Center, The Wistar Institute, Philadelphia, Pennsylvania.
Mizuho Fukunaga-KalabisMolecular and Cellular Oncogenesis Program and Melanoma Research Center, The Wistar Institute, Philadelphia, Pennsylvania.
Clemens KreplerMolecular and Cellular Oncogenesis Program and Melanoma Research Center, The Wistar Institute, Philadelphia, Pennsylvania.
Pedro Aza-BlancTumor Initiation and Maintenance Program, Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California.
Chih-Cheng YangTumor Initiation and Maintenance Program, Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California.
Bela DelvadiaMolecular and Cellular Oncogenesis Program and Melanoma Research Center, The Wistar Institute, Philadelphia, Pennsylvania.
Cynthia TongMolecular and Cellular Oncogenesis Program and Melanoma Research Center, The Wistar Institute, Philadelphia, Pennsylvania.
Ye HuangMolecular and Cellular Oncogenesis Program and Melanoma Research Center, The Wistar Institute, Philadelphia, Pennsylvania.
Maya DelvadiaMolecular and Cellular Oncogenesis Program and Melanoma Research Center, The Wistar Institute, Philadelphia, Pennsylvania.
Alice S MoriasMolecular and Cellular Oncogenesis Program and Melanoma Research Center, The Wistar Institute, Philadelphia, Pennsylvania.ORCID 0000-0003-0371-2102
Katrin SproesserMolecular and Cellular Oncogenesis Program and Melanoma Research Center, The Wistar Institute, Philadelphia, Pennsylvania.
Patricia BraffordMolecular and Cellular Oncogenesis Program and Melanoma Research Center, The Wistar Institute, Philadelphia, Pennsylvania.
Joshua X WangMolecular and Cellular Oncogenesis Program and Melanoma Research Center, The Wistar Institute, Philadelphia, Pennsylvania.
Marilda BeqiriMolecular and Cellular Oncogenesis Program and Melanoma Research Center, The Wistar Institute, Philadelphia, Pennsylvania.
Rajasekharan SomasundaramMolecular and Cellular Oncogenesis Program and Melanoma Research Center, The Wistar Institute, Philadelphia, Pennsylvania.
Adina VulturMolecular and Cellular Oncogenesis Program and Melanoma Research Center, The Wistar Institute, Philadelphia, Pennsylvania.ORCID 0000-0003-0068-9496
Denitsa M HristovaMolecular and Cellular Oncogenesis Program and Melanoma Research Center, The Wistar Institute, Philadelphia, Pennsylvania.
Lawrence W WuMolecular and Cellular Oncogenesis Program and Melanoma Research Center, The Wistar Institute, Philadelphia, Pennsylvania.
Yiling LuDepartment of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Gordon B MillsDepartment of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0002-0144-9614
Wei XuAbramson Cancer Center, Department of Medicine, Hospital of the University of Pennsylvania, University of Pennsylvania, Philadelphia, Pennsylvania.
Giorgos C KarakousisDepartment of Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.
Xiaowei XuDepartment of Pathology and Laboratory Medicine, Hospital of University of Pennsylvania, Philadelphia, Pennsylvania.ORCID 0000-0003-4098-7690
Lynn M SchuchterAbramson Cancer Center, Department of Medicine, Hospital of the University of Pennsylvania, University of Pennsylvania, Philadelphia, Pennsylvania.
Tara C MitchellAbramson Cancer Center, Department of Medicine, Hospital of the University of Pennsylvania, University of Pennsylvania, Philadelphia, Pennsylvania.
Ravi K AmaravadiAbramson Cancer Center, Department of Medicine, Hospital of the University of Pennsylvania, University of Pennsylvania, Philadelphia, Pennsylvania.
Lawrence N KwongDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Dennie T FrederickDivision of Surgical Oncology, Massachusetts General Hospital Cancer Center, Boston, Massachusetts.
Genevieve M BolandDivision of Surgical Oncology, Massachusetts General Hospital Cancer Center, Boston, Massachusetts.ORCID 0000-0002-7522-6173
Joseph M SalvinoMolecular and Cellular Oncogenesis Program and Melanoma Research Center, The Wistar Institute, Philadelphia, Pennsylvania.ORCID 0000-0002-2184-5980
David W SpeicherMolecular and Cellular Oncogenesis Program and Melanoma Research Center, The Wistar Institute, Philadelphia, Pennsylvania.
Keith T FlahertyDepartment of Medicine, Harvard Medical School, Boston, Massachusetts.
Ze'ev A RonaiTumor Initiation and Maintenance Program, Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California.ORCID 0000-0002-3859-0400
Meenhard HerlynMolecular and Cellular Oncogenesis Program and Melanoma Research Center, The Wistar Institute, Philadelphia, Pennsylvania. herlynm@wistar.org.
The Wistar Institute · USHospital of the University of Pennsylvania · USDiscovery Institute · USNew Jersey Institute of Technology · USThe University of Texas MD Anderson Cancer Center · USMassachusetts General Hospital · USHarvard University · US
Funding
Women's Cancer Research ProgramP30CA014236 · NCI · DUKE UNIVERSITY · PI Laura Fish · 1985 to 2026
$174.8MTumor Microenvironment and Cancer ImmunologyP30CA030199 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI ELENA B PASQUALE · 1985 to 2026
$107.2MTumor Microenvironment and MetastasisP30CA010815 · NCI · WISTAR INSTITUTE · PI Aaron Robert Goldman · 1985 to 2026
$75.9MTargeting the MAP and PI3 Kinase Pathways in MelanomaP01CA114046 · NCI · WISTAR INSTITUTE · PI HERLYN, MEENHARD F · 2008 to 2023
$37.1MTUMOR DEVELOPMENT AND PROGRESSION IN HUMAN MELANOCYTESP01CA025874 · NCI · WISTAR INSTITUTE · PI HERLYN, MEENHARD F · 1985 to 2015
$19.0MResearch Project 2 - Targeting Melanoma Tumor Survival and Apoptotic MachineryU54CA224070 · NCI · WISTAR INSTITUTE · PI Michael Davies · 2017 to 2026
$13.9MMETASTATIS: BIOLOGICAL PHENOTYPE AND MODELS FOR THERAPYR01CA047159 · NCI · WISTAR INSTITUTE · PI HERLYN, MEENHARD F · 1989 to 2015
$3.9MThe role of genetic susceptibility in melanoma developmentR01CA182890 · NCI · WISTAR INSTITUTE · PI HERLYN, MEENHARD F · 2014 to 2018
$2.1MIntegrative Approach to Comprehensive Analysis of High Throughput Data on a Cancer Center LevelR50CA211199 · NCI · WISTAR INSTITUTE · PI Andrew V Kossenkov · 2016 to 2026
$1.6MPurchase of a Q Exactive HF mass spectrometer system for metabolomicsS10OD023586 · OD · WISTAR INSTITUTE · PI SPEICHER, DAVID W. · 2017 to 2017
$600kDissecting clonal diversity in melanoma to overcome therapy resistance andmetastasisK01CA245124 · NCI · JOHNS HOPKINS UNIVERSITY · PI REBECCA, VITO WILLIAM · 2020 to 2024
$595kNCI NIH HHS K01 CA245124NCI NIH HHS P01 CA025874NCI NIH HHS P01 CA114046NCI NIH HHS P30 CA010815NCI NIH HHS P30 CA014236NCI NIH HHS P30 CA030199NCI NIH HHS R01 CA047159NCI NIH HHS R01 CA182890NCI NIH HHS R50 CA211199NCI NIH HHS U54 CA224070NIH HHS S10 OD023586
Abstract
Metastatic melanoma is challenging to clinically address. Although standard-of-care targeted therapy has high response rates in patients with BRAF-mutant melanoma, therapy relapse occurs in most cases. Intrinsically resistant melanoma cells drive therapy resistance and display molecular and biologic properties akin to neural crest-like stem cells (NCLSC) including high invasiveness, plasticity, and self-renewal capacity. The shared transcriptional programs and vulnerabilities between NCLSCs and cancer cells remains poorly understood. Here, we identify a developmental LPAR1-axis critical for NCLSC viability and melanoma cell survival. LPAR1 activity increased during progression and following acquisition of therapeutic resistance. Notably, genetic inhibition of LPAR1 potentiated BRAFi ± MEKi efficacy and ablated melanoma migration and invasion. Our data define LPAR1 as a new therapeutic target in melanoma and highlights the promise of dissecting stem cell-like pathways hijacked by tumor cells. SIGNIFICANCE: This study identifies an LPAR1-axis critical for melanoma invasion and intrinsic/acquired therapy resistance.
Indexed as
Drug Resistance, NeoplasmGene Expression Regulation, NeoplasticAnimalsAntineoplastic AgentsApoptosisBiomarkers, TumorCell ProliferationHumansMelanomaMiceMice, Inbred NODMice, SCIDNeural CrestNeural Stem CellsPrognosisReceptors, Lysophosphatidic AcidAntineoplastic AgentsBiomarkers, TumorLPAR1 protein, humanReceptors, Lysophosphatidic Acid
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