ArticleMolecular cancer2017
Reprogramming of stromal fibroblasts by SNAI2 contributes to tumor desmoplasia and ovarian cancer progression.
Article in Molecular cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 73 citations in OpenAlex.
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- Role of SLC7A11/xCT in Ovarian Cancer.International journal of molecular sciences · 2024Review
- SNAI2 as a Prognostic Biomarker Based on Cancer-Associated Fibroblasts in Patients With Lung Adenocarcinoma.Clinical Medicine Insights. Oncology · 2024Article
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- The recent advancements of ferroptosis in the diagnosis, treatment and prognosis of ovarian cancer.Frontiers in genetics · 2023Review
- Cancer-associated fibroblasts in gynecological malignancies: are they really allies of the enemy?Frontiers in oncology · 2023Review
- CRMP2 derived from cancer associated fibroblasts facilitates progression of ovarian cancer via HIF-1α-glycolysis signaling pathway.Cell death & disease · 2022Article
- Dynamic expression of SNAI2 in prostate cancer predicts tumor progression and drug sensitivity.Molecular oncology · 2022Article
- SNAI2 promotes the development of ovarian cancer through regulating ferroptosis.Bioengineered · 2022Article
- GLIS1 in Cancer-Associated Fibroblasts Regulates the Migration and Invasion of Ovarian Cancer Cells.International journal of molecular sciences · 2022Article
- UCP1 modulates immune infiltration level and survival outcome in ovarian cancer patients.Journal of ovarian research · 2022Article
- Ferroptosis: A New Promising Target for Ovarian Cancer Therapy.International journal of medical sciences · 2022Review
- The potential value of cuprotosis (copper-induced cell death) in the therapy of clear cell renal cell carcinoma.American journal of cancer research · 2022Article
- Effect of unfolded protein response on the immune infiltration and prognosis of transitional cell bladder cancer.Annals of medicine · 2021Article
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMolecular profiling in ovarian cancer (OC) revealed that the desmoplasia subtype presented the poorest prognosis, highlighting the contribution of stromal fibroblasts in tumor progression. This study aimed to investigate the molecular characteristics of SNAI2 driving the transcriptional reprogramming of fibroblasts within tumors.
methodsSNAI2 expression was evaluated in microdissected profiles of various cancers and in various molecular subtypes of OC. Gene set enrichment analysis (GSEA) and single sample GSEA (ssGSEA) were performed to explore the correlation between SNAI2 and stromal fibroblast activation. The SNAI2 defined signature in the mesenchymal OC subtype was identified through an integrative analysis of the TCGA and the Tothill datasets. The predictive value of this signature was validated in independent datasets. SNAI2 expression alteration influence of tumor growth in primary CAFs was evaluated in 3D organotypic and murine xenograft models.
resultsWe demonstrated that SNAI2 was frequently activated in the tumor stroma, correlated with fibroblast activation and worse patient outcome in OC. SNAI2 transformed normal fibroblasts to a CAF-like state and boosted their tumor-supporting role in 3D organotypic culture and in OC xenograft model. SNAI2 drove a transcriptional signature in the mesenchymal subtype of OC that contributed to tumor desmoplasia, which fed back to increase SNAI2 expression and sustain fibroblast activation.
conclusionsOur results address the role of SNAI2 in reprogramming stromal fibroblasts. The identified SNAI2 mesenchymal signature has both a predictive value and biological relevance and might be a therapeutic target for stroma-oriented therapy against the desmoplasia OC subtype.
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