ArticleThe Journal of clinical investigation2020
PIK3Cδ expression by fibroblasts promotes triple-negative breast cancer progression.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed, 51 citations in OpenAlex.
- Unveiling the Impact of Copper Metabolism on Epithelial-Mesenchymal Transition of Triple-Negative Breast Cancer: Identification of Therapeutic Targets.Interdisciplinary sciences, computational life sciences · 2026Article
- Spatial organization of the TNBC tumor microenvironment: multicellular niches, T-cell bottlenecks, and therapeutic opportunities.Journal of translational medicine · 2026Review
- Cancer-associated fibroblasts as key regulators of lipid metabolism in the tumour microenvironment.Oncogene · 2026Review
- Identification and validation of a refined CAF-Associated diagnostic signature in breast cancer.Scientific reports · 2026Article
- Spleen tyrosine kinase (SYK) inhibition suppresses growth of gastrointestinal neuroendocrine tumor cells: a pilot study in two cell lines.Cancer gene therapy · 2025Article
- CAFs exosomal circFOXO1 promotes TNBC autophagy and radioresistance via miR-27a-3p/BNIP3 axis.Scientific reports · 2025Article
- Stromal PLAU mediates tumor progression and informs a novel therapeutic target in triple-negative breast cancer.Cancer cell international · 2025Article
- FAK inhibition disrupts tumor growth, apoptosis, and transcriptional regulation in GI-NETs.Endocrine oncology (Bristol, England) · 2025Article
- Kinome-Wide Synthetic Lethal Screen Identifies PANK4 as a Modulator of Temozolomide Resistance in Glioblastoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Integrative analysis with machine learning identifies diagnostic and prognostic signatures in neuroblastoma based on differentially DNA methylated enhancers between INSS stage 4 and 4S neuroblastoma.Journal of cancer research and clinical oncology · 2024Article
- JAK3/STAT5 signaling-triggered upregulation of PIK3CD contributes to gastric carcinoma development.Journal of cell communication and signaling · 2024Article
- Characterization of cancer-associated fibroblasts (CAFs) and development of a CAF-based risk model for triple-negative breast cancer.Cancer cell international · 2023Article
- PIK3CD correlates with prognosis, epithelial-mesenchymal transition and tumor immune infiltration in breast carcinoma.Discover oncology · 2023Article
- Estrogen receptor status heterogeneity in breast cancer tumor: role in response to endocrine treatment.Cancer gene therapy · 2023Article
- Proteins Found in the Triple-Negative Breast Cancer Secretome and Their Therapeutic Potential.International journal of molecular sciences · 2023Review
- The importance of cancer-associated fibroblasts in targeted therapies and drug resistance in breast cancer.Frontiers in oncology · 2023Review
- An integrated map of fibroblastic populations in human colon mucosa and cancer tissues.Communications biology · 2022Article
- The tumor microenvironment and triple-negative breast cancer aggressiveness: shedding light on mechanisms and targeting.Expert opinion on therapeutic targets · 2022Article
- Knockdown of NCOR2 Inhibits Cell Proliferation via BDNF/TrkB/ERK in NF1-Derived MPNSTs.Cancers · 2022Article
- Tumour stroma ratio is a potential predictor for 5-year disease-free survival in breast cancer.BMC cancer · 2022Article
Corrections and comments
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Authors and funding
27 authors at 10 institutions in 6 countries.
Funding
Abstract
As there is growing evidence for the tumor microenvironment's role in tumorigenesis, we investigated the role of fibroblast-expressed kinases in triple-negative breast cancer (TNBC). Using a high-throughput kinome screen combined with 3D invasion assays, we identified fibroblast-expressed PIK3Cδ (f-PIK3Cδ) as a key regulator of cancer progression. Although PIK3Cδ was expressed in primary fibroblasts derived from TNBC patients, it was barely detectable in breast cancer (BC) cell lines. Genetic and pharmacological gain- and loss-of-function experiments verified the contribution of f-PIK3Cδ in TNBC cell invasion. Integrated secretomics and transcriptomics analyses revealed a paracrine mechanism via which f-PIK3Cδ confers its protumorigenic effects. Inhibition of f-PIK3Cδ promoted the secretion of factors, including PLGF and BDNF, that led to upregulation of NR4A1 in TNBC cells, where it acts as a tumor suppressor. Inhibition of PIK3Cδ in an orthotopic BC mouse model reduced tumor growth only after inoculation with fibroblasts, indicating a role of f-PIK3Cδ in cancer progression. Similar results were observed in the MMTV-PyMT transgenic BC mouse model, along with a decrease in tumor metastasis, emphasizing the potential immune-independent effects of PIK3Cδ inhibition. Finally, analysis of BC patient cohorts and TCGA data sets identified f-PIK3Cδ (protein and mRNA levels) as an independent prognostic factor for overall and disease-free survival, highlighting it as a therapeutic target for TNBC.
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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 Socratic graph.