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Updated: Aug 6, 2026

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
06:09

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells

Published on: June 7, 2019

Autocrine CysLT1R-ERK/YAP signaling drives melanoma progression and reveals a targetable oncogenic GPCR axis

Emma Elizabeth Sabu Kattuman1, Lakshminarayan Reddy Teegala1, Venkatesh Katari1

  • 1Department of Physiology and Pharmacology, The University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA.

Oncogene
|July 24, 2026
PubMed

Insights

The cysteinyl leukotriene receptor 1 (CysLT1R) drives melanoma progression by activating YAP and ERK pathways. Inhibiting CysLT1R shows promise for treating this lethal skin cancer.

Area of Science:

  • Oncology
  • Dermatology
  • Molecular Biology

Background:

  • Cutaneous melanoma is a lethal skin cancer with significant tumor heterogeneity.
  • Therapeutic resistance is a major challenge in melanoma treatment.

Purpose of the Study:

  • To identify novel drivers of melanoma progression.
  • To investigate the role of cysteinyl leukotriene receptor 1 (CysLT1R) in melanoma.
  • To explore CysLT1R as a potential therapeutic target.

Main Methods:

  • Analysis of The Cancer Genome Atlas (TCGA) datasets.
  • Functional studies in murine and human melanoma cells.
  • In vivo studies using genetic ablation and pharmacological inhibition (MK571).
  • Investigation of signaling pathways including YAP, ERK, and LOXL-2.

Main Results:

  • CysLT1R transcript levels are elevated in metastatic melanoma.
  • Leukotriene D4 (LTD4)-mediated CysLT1R activation promotes melanoma cell proliferation and invasion via YAP and ERK.
  • Melanoma cells exhibit an autocrine CysLT1R signaling loop.
  • Inhibition of CysLT1R attenuates tumor growth and inhibits the YAP-LOXL-2 axis.
  • Host CysLT1R signaling contributes to melanoma progression.

Conclusions:

  • CysLT1R is a previously unrecognized driver of cutaneous melanoma.
  • A CysLT1R-ERK/YAP,LOXL-2 signaling circuit promotes melanoma progression.
  • CysLT1R represents a potential therapeutic target for melanoma.

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