Decoding the S1P‑S1PR axis in cancer: Mechanisms, pathways and therapeutic horizons (Review)
Journal
Biomedical Reports
Journal Volume
25
Journal Issue
1
Start Page
1
End Page
11
ISSN
2049-9434
2049-9442
Date Issued
2026-05-04
Author(s)
Abstract
Sphingosine‑1‑phosphate (S1P) and its five G protein‑coupled receptors (S1PR1‑S1PR5) regulate a broad range of processes that shape cancer progression, including proliferation, survival, angiogenesis, immune evasion and metastatic dissemination. Under physiological conditions, this signaling axis contributes to vascular integrity, immune cell trafficking and tissue homeostasis. In cancer, however, its output is not solely determined by ligand abundances. Rather, tumors reprogram the S1P‑S1PR axis at a number of levels, coupling altered S1P production with receptor‑specific changes in expression, localization and the signaling state to generate context‑dependent malignant phenotypes. The present review provided a receptor‑resolved synthesis of S1PR functions in cancer and examined the mechanisms that underlie pathway dysregulation, including transcrip‑ tional activation, epigenetic remodeling, microRNA loss, post‑translational modifications and altered receptor traf‑ ficking and compartmentalization. It further discussed how metabolic amplification of S1P availability cooperates with receptor‑level rewiring to sustain tumor progression, microenvironmental remodeling and therapeutic resistance. This framework positions the S1P‑S1PR axis as a dynami‑ cally reprogrammed signaling network and highlights therapeutic strategies that concurrently target S1P production and receptor‑mediated signaling as promising avenues for more‑precise, biomarker‑informed cancer treatment.
Subjects
cancer progression
sphingosine‑1‑ phosphate‑targeted therapy
sphingosine‑1‑phosphate
sphingosine‑1‑phosphate receptor
tumor microenvironment
Publisher
Spandidos Publications
Description
Article number: 80
Type
review article