ArticleOncogene2016
Hyperactivated FRS2α-mediated signaling in prostate cancer cells promotes tumor angiogenesis and predicts poor clinical outcome of patients.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- Article
- Crosstalk between Endothelial Cells and Tumor Cells: A New Era in Prostate Cancer Progression.International journal of molecular sciences · 2023Review
- Tephrosin Suppresses the Chemoresistance of Paclitaxel-Resistant Ovarian Cancer via Inhibition of FGFR1 Signaling Pathway.Biomedicines · 2023Article
- Discovery of a small molecule ligand of FRS2 that inhibits invasion and tumor growth.Cellular oncology (Dordrecht, Netherlands) · 2023Article
- A novel risk score model based on five angiogenesis-related long non-coding RNAs for bladder urothelial carcinoma.Cancer cell international · 2022Article
- miRNA-34b/c regulates mucus secretion in RSV-infected airway epithelial cells by targeting FGFR1.Journal of cellular and molecular medicine · 2021Article
- Post-Translational Modifications That Drive Prostate Cancer Progression.Biomolecules · 2021Review
- Fibroblast growth factors signaling in bone metastasis.Endocrine-related cancer · 2020Review
- Influence of SHH/GLI1 axis on EMT mediated migration and invasion of breast cancer cells.Scientific reports · 2019Article
- Whole-genome sequencing identifies ADGRG6 enhancer mutations and FRS2 duplications as angiogenesis-related drivers in bladder cancer.Nature communications · 2019Article
- Fibroblast Growth Factor Family in the Progression of Prostate Cancer.Journal of clinical medicine · 2019Review
- Upregulation of MicroRNA-21 promotes tumorigenesis of prostate cancer cells by targeting KLF5.Cancer biology & therapy · 2019Article
- Intrinsic FGFR2 and Ectopic FGFR1 Signaling in the Prostate and Prostate Cancer.Frontiers in genetics · 2019Review
- Offsetting Expression Profiles of Prognostic Markers in Prostate Tumor vs. Its Microenvironment.Frontiers in oncology · 2019Article
- Ectopic fibroblast growth factor receptor 1 promotes inflammation by promoting nuclear factor-κB signaling in prostate cancer cells.The Journal of biological chemistry · 2018Article
- Prostate Organogenesis.Cold Spring Harbor perspectives in medicine · 2018Review
- FGF19 genetic amplification as a potential therapeutic target in lung squamous cell carcinomas.Thoracic cancer · 2017Article
- DHX32 Promotes Angiogenesis in Colorectal Cancer Through Augmenting β-catenin Signaling to Induce Expression of VEGFA.EBioMedicine · 2017Article
- Combination treatment of prostate cancer with FGF receptor and AKT kinase inhibitors.Oncotarget · 2017Article
- Fibroblast growth factors, old kids on the new block.Seminars in cell & developmental biology · 2016Review
Corrections and comments
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Authors and funding
15 authors at 8 institutions in 3 countries.
Funding
Abstract
Metastasis of tumors requires angiogenesis, which is comprised of multiple biological processes that are regulated by angiogenic factors. The fibroblast growth factor (FGF) is a potent angiogenic factor and aberrant FGF signaling is a common property of tumors. Yet, how the aberration in cancer cells contributes to angiogenesis in the tumor is not well understood. Most studies of its angiogenic signaling mechanisms have been in endothelial cells. FGF receptor substrate 2α (FRS2α) is an FGF receptor-associated protein required for activation of downstream signaling molecules that include those in the mitogen-activated protein and AKT kinase pathways. Herein, we demonstrated that overactivation and hyperactivity of FRS2α, as well as overexpression of cJUN and HIF1α, were positively correlated with vessel density and progression of human prostate cancer (PCa) toward malignancy. We also demonstrate that FGF upregulated the production of vascular endothelial growth factor A mainly by increasing expression of cJUN and HIF1α. This then promoted recruitment of endothelial cells and vessel formation for the tumor. Tumor angiogenesis in mouse PCa tissues was compromised by tissue-specific ablation of Frs2α in prostate epithelial cells. Depletion of Frs2α expression in human PCa cells and in a preclinical xenograft model, MDA PCa 118b, also significantly suppressed tumor angiogenesis accompanied with decreased tumor growth in the bone. The results underscore the angiogenic role of FRS2α-mediated signaling in tumor epithelial cells in angiogenesis. They provide a rationale for treating PCa with inhibitors of FGF signaling. They also demonstrate the potential of overexpressed FRS2α as a biomarker for PCa diagnosis, prognosis and response to therapies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.