Carboxylesterase 1-mediated endocannabinoid metabolism in skin: role in melanoma progression in BRaf^V600E/Pten^-/- mice.

ABSTRACT:

Background

Melanoma is a highly aggressive skin cancer with a poor prognosis. The endocannabinoids 2-arachidonoylgylcerol (2-AG) and anandamide have been linked to melanoma progression, though their roles remain unclear. We hypothesized that the 2-AG-arachidonate-prostaglandin axis could drive aggressive melanoma progression.

Methods

The genetically engineered melanoma mouse model B6-Tyr::CreER^T2; BRaf^CA; Pten^loxP was characterized by targeted metabolomics. Functionally expressed serine hydrolases in the tumor tissue were identified by chemoproteomics. Pharmacological inhibition of carboxylesterase 1 (CES1) was achieved through chronic in vivo i.p. treatment with JZL184 (10 mg/kg daily), confirmed by activity-based protein profiling (ABPP) an

SUBMITTER: Morozova V 

PROVIDER: S-EPMC11817774 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature