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Article: Neural Crest-Like Stem Cell Transcriptome Analysis Identifies LPAR1 in Melanoma Progression and Therapy Resistance

TitleNeural Crest-Like Stem Cell Transcriptome Analysis Identifies LPAR1 in Melanoma Progression and Therapy Resistance
Authors
Issue Date2021
Citation
Cancer Research, 2021, v. 81, n. 20, p. 5230-5241 How to Cite?
AbstractMetastatic 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.
Persistent Identifierhttp://hdl.handle.net/10722/318957
ISSN
2021 Impact Factor: 13.312
2020 SCImago Journal Rankings: 4.103
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLiu, Jianglan-
dc.contributor.authorRebecca, Vito W.-
dc.contributor.authorKossenkov, Andrew V.-
dc.contributor.authorConnelly, Thomas-
dc.contributor.authorLiu, Qin-
dc.contributor.authorGutierrez, Alexis-
dc.contributor.authorXiao, Min-
dc.contributor.authorLi, Ling-
dc.contributor.authorZhang, Gao-
dc.contributor.authorSamarkina, Anastasia-
dc.contributor.authorZayasbazan, Delaine-
dc.contributor.authorZhang, Jie-
dc.contributor.authorCheng, Chaoran-
dc.contributor.authorWei, Zhi-
dc.contributor.authorAlicea, Gretchen M.-
dc.contributor.authorFukunaga-Kalabis, Mizuho-
dc.contributor.authorKrepler, Clemens-
dc.contributor.authorAza-Blanc, Pedro-
dc.contributor.authorYang, Chih Cheng-
dc.contributor.authorDelvadia, Bela-
dc.contributor.authorTong, Cynthia-
dc.contributor.authorHuang, Ye-
dc.contributor.authorDelvadia, Maya-
dc.contributor.authorMorias, Alice S.-
dc.contributor.authorSproesser, Katrin-
dc.contributor.authorBrafford, Patricia-
dc.contributor.authorWang, Joshua X.-
dc.contributor.authorBeqiri, Marilda-
dc.contributor.authorSomasundaram, Rajasekharan-
dc.contributor.authorVultur, Adina-
dc.contributor.authorHristova, Denitsa M.-
dc.contributor.authorWu, Lawrence W.-
dc.contributor.authorLu, Yiling-
dc.contributor.authorMills, Gordon B.-
dc.contributor.authorXu, Wei-
dc.contributor.authorKarakousis, Giorgos C.-
dc.contributor.authorXu, Xiaowei-
dc.contributor.authorSchuchter, Lynn M.-
dc.contributor.authorMitchell, Tara C.-
dc.contributor.authorAmaravadi, Ravi K.-
dc.contributor.authorKwong, Lawrence N.-
dc.contributor.authorFrederick, Dennie T.-
dc.contributor.authorBoland, Genevieve M.-
dc.contributor.authorSalvino, Joseph M.-
dc.contributor.authorSpeicher, David W.-
dc.contributor.authorFlaherty, Keith T.-
dc.contributor.authorRonai, Ze'ev A.-
dc.contributor.authorHerlyn, Meenhard-
dc.date.accessioned2022-10-11T12:24:56Z-
dc.date.available2022-10-11T12:24:56Z-
dc.date.issued2021-
dc.identifier.citationCancer Research, 2021, v. 81, n. 20, p. 5230-5241-
dc.identifier.issn0008-5472-
dc.identifier.urihttp://hdl.handle.net/10722/318957-
dc.description.abstractMetastatic 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.-
dc.languageeng-
dc.relation.ispartofCancer Research-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleNeural Crest-Like Stem Cell Transcriptome Analysis Identifies LPAR1 in Melanoma Progression and Therapy Resistance-
dc.typeArticle-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1158/0008-5472.CAN-20-1496-
dc.identifier.pmid34462276-
dc.identifier.pmcidPMC8530965-
dc.identifier.scopuseid_2-s2.0-85117719587-
dc.identifier.volume81-
dc.identifier.issue20-
dc.identifier.spage5230-
dc.identifier.epage5241-
dc.identifier.eissn1538-7445-
dc.identifier.isiWOS:000709594700010-

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