Neural Crest-Like Stem Cell Transcriptome Analysis Identifies LPAR1 in Melanoma Progression and Therapy Resistance
Document Type
Article
Publication Date
10-15-2021
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.
Identifier
85117719587 (Scopus)
Publication Title
Cancer Research
External Full Text Location
https://doi.org/10.1158/0008-5472.CAN-20-1496
e-ISSN
15387445
ISSN
00085472
PubMed ID
34462276
First Page
5230
Last Page
5241
Issue
20
Volume
81
Grant
CA010815
Fund Ref
National Institutes of Health
Recommended Citation
Liu, Jianglan; Rebecca, Vito W.; Kossenkov, Andrew V.; Connelly, Thomas; Liu, Qin; Gutierrez, Alexis; Xiao, Min; Li, Ling; Zhang, Gao; Samarkina, Anastasia; Zayasbazan, Delaine; Zhang, Jie; Cheng, Chaoran; Wei, Zhi; Alicea, Gretchen M.; Fukunaga-Kalabis, Mizuho; Krepler, Clemens; and Aza-Blanc, Pedro, "Neural Crest-Like Stem Cell Transcriptome Analysis Identifies LPAR1 in Melanoma Progression and Therapy Resistance" (2021). Faculty Publications. 3740.
https://digitalcommons.njit.edu/fac_pubs/3740
