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Sphingosine-1-phosphate receptor 1 promotes ovarian cancer tumorsphere proliferation and metastasis

ABSTRACT: Despite extensive clinical endeavors to enhance high-grade serous ovarian cancer (HGSOC) detection and treatment, an alarming half of diagnosed women succumb annually to this disease. Significantly, nearly all HGSOC cases manifest ascites at diagnosis, a poor prognostic indicator. Malignant ascites production arises as ovarian cancer cells shed from the primary tumor, creating a hostile environment that endangers their survival. Consequently, cancer cells aggregate into tumorspheres, the principal metastatic units in HGSOC. The molecular mechanisms that tumorspheres use to overcome the ascites bottleneck and metastasize are still poorly understood. Studying tumorspheres isolated from ascites samples from treatment naïve HGSOC patients, as well as three-dimensional spheroid in vitro and in vivo ovarian cancer cell models, we report that the Sphingosine-1-Phosphate (S1P) ligand and its receptor S1PR1 axis is especially relevant in ovarian tumorspheres, where it promotes an autocrine positive loop, serving as their primary proliferative mechanism via MEK1/2-ERK activation. Our findings demonstrate that the S1P-S1PR1-MEK1/2 pathway confers ovarian tumorspheres a selective advantage within the ascites environment and, consequently, increases their metastatic potential.

INSTRUMENT(S): Liquid Chromatography MS - alternating - reverse phase, Liquid Chromatography MS - positive - reverse phase

PROVIDER: MTBLS13770 | MetaboLights | 2026-03-04

REPOSITORIES: MetaboLights

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			Action	DRS
	Lipidomics_Gendrau_et_al_1.xlsx	Xlsx
	Lipidomics_Gendrau_et_al_2.xlsx	Xlsx
	a_MTBLS13770_LC-MS_alternating_reverse-phase_metabolite_profiling.txt	Txt
	a_MTBLS13770_LC-MS_positive_reverse-phase_metabolite_profiling-1.txt	Txt
	i_Investigation.txt	Txt

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