Authors
Emma Elizabeth Sabu Kattuman, Lakshminarayan Reddy Teegala, Venkatesh Katari, Somayeh Darzi, Srinivas Vinod Saladi, Ivana de la Serna, Charles K Thodeti, Sailaja Paruchuri
Published in
Oncogene. Jul 24, 2026. Epub Jul 24, 2026.
Abstract
Cutaneous melanoma remains the most lethal skin cancer due to profound tumor heterogeneity and the frequent development of resistance to current therapies. Here, we identify the cysteinyl leukotriene receptor 1 (CysLT1R) as a previously unrecognized driver of melanoma progression. Analysis of bulk RNA-sequencing datasets from The Cancer Genome Atlas (TCGA) revealed significantly elevated CysLT1R transcript in metastatic tumors compared to primary tumors. Functional studies in murine and human melanoma cells demonstrated that leukotriene D4 (LTD4)-mediated activation of CysLT1R promotes melanoma cell proliferation and invasion through the parallel engagement of YAP and ERK signaling pathways. Notably, melanoma cells express LTC4 synthase and secrete cysteinyl leukotrienes, establishing a constitutive autocrine signaling loop that sustains CysLT1R activity independently of the host niche. Genetic ablation or pharmacological inhibition of CysLT1R with MK571 significantly attenuated tumor growth in vivo and was associated with inhibition of the YAP-LOXL-2 signaling axis. In addition, studies using Cysltr1-/- mice reveal that host-derived CysLT1R signaling within the tumor microenvironment also contributes to melanoma progression. Together, these findings uncover a previously unrecognized pro-tumorigenic CysLT1R-ERK/YAP,LOXL-2 signaling circuit that promotes cutaneous melanoma progression and highlight CysLT1R as a potential therapeutic target for melanoma.
PMID:
42498732
Bibliographic data and abstract were imported from PubMed on 25 Jul 2026.
Read full publication at:
Please sign in
to see all details.
Advertisement
Stats
- Recommendations n/a n/a positive of 0 vote(s)
- Views 11
- Comments 0