Related Experiment Video
Updated: May 18, 2026
Murine Model for Non-invasive Imaging to Detect and Monitor Ovarian Cancer Recurrence
Published on: November 2, 2014
Single-cell and spatial analyses identify a glycolysis-high state driven by STOML2 in epithelial ovarian cancer
Lijing Liu1, Baohong Ren1, Yinxing Zhu2
1Department of Gynecology, Wuxi Hospital Affiliated to Nanjing University of Chinese Medicine, Wuxi, 214000, China.
Objective:
Metabolic heterogeneity contributes to therapeutic resistance and poor prognosis in epithelial ovarian cancer (EOC), yet the regulatory drivers of aggressive glycolytic states remain incompletely defined. We aimed to delineate glycolysis-associated malignant epithelial states and identify actionable regulatory hubs.
Methods:
We integrated single-cell RNA sequencing with spatial transcriptomics to map metabolic programmes in the ovarian cancer microenvironment. High-dimensional weighted gene co-expression network analysis (hdWGCNA) and differential expression analyses were used to nominate glycolysis-associated modules and hub candidates. A multi-cohort machine-learning framework was applied to construct and validate a prognostic signature using TCGA-OV and independent GEO cohorts. STOML2 was functionally validated in A2780 and SKOV3 cells using gain- and loss-of-function approaches, phenotypic assays, Seahorse extracellular flux analysis, and pharmacological modulation of AKT/mTOR signalling.
Results:
Single-cell analyses identified a malignant epithelial subpopulation with high glycolytic activity (HGS) and spatial transcriptomics confirmed heterogeneous enrichment of glycolysis-high regions within tumour areas. HdWGCNA prioritised a glycolysis-linked module, from which STOML2 emerged as a central hub. A STOML2-containing prognostic signature robustly stratified risk across multiple cohorts. Experimentally, STOML2 promoted proliferation, clonogenicity, migration and invasion, suppressed apoptosis, and enhanced glycolytic output (increased glucose uptake, lactate production and ECAR) with reciprocal changes in respiratory activity. Mechanistically, STOML2 activated AKT and mTOR phosphorylation; AKT activation partially rescued the metabolic and growth defects induced by STOML2 knockdown, whereas AKT inhibition blunted STOML2-driven glycolysis and malignant phenotypes.
Conclusion:
STOML2 links a glycolysis-high malignant epithelial state to AKT/mTOR-dependent metabolic reprogramming and tumour aggressiveness in EOC. These findings support STOML2 as a prognostic biomarker and a potential therapeutic vulnerability in metabolically aggressive ovarian tumours.
