ArticleInternational journal of cancer2020
The GEF-H1/PKD3 signaling pathway promotes the maintenance of triple-negative breast cancer stem cells.
Article in International journal of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- Research Progress on the ARHGEF Family in Cardiovascular Diseases.Cell biochemistry and function · 2026Review
- Article
- Guanine Nucleotide Exchange Factors and Small GTPases: Their Regulation and Functions, Diseases, and Therapeutic Targets.MedComm · 2025Review
- PKD3 localizes to late endosomes to maintain Rab7-dependent endolysosomal homeostasis.iScience · 2025Article
- Reciprocal regulation of Solo and Src orchestrates Src trafficking to promote mesenchymal cell migration.iScience · 2025Article
- Protein kinase D drives the secretion of invasion mediators in triple-negative breast cancer cell lines.iScience · 2024Article
- PRKD3 promotes proliferation of liver cancer cells: a downstream proteomics profiling study.American journal of translational research · 2024Article
- Small Molecule Inhibitors of Protein Kinase D: Early Development, Current Approaches, and Future Directions.Journal of medicinal chemistry · 2023Review
- Membrane trafficking in breast cancer progression: protein kinase D comes into play.Frontiers in cell and developmental biology · 2023Review
- Androgen deprivation restores ARHGEF2 to promote neuroendocrine differentiation of prostate cancer.Cell death & disease · 2022Article
- Therapeutic Validation of GEF-H1 Using a De Novo Designed Inhibitor in Models of Retinal Disease.Cells · 2022Article
- Dysfunctional EGFR and oxidative stress-induced PKD1 signaling drive formation of DCLK1+ pancreatic stem cells.iScience · 2021Article
- Regulation of cancer stem cells in triple negative breast cancer.Cancer drug resistance (Alhambra, Calif.) · 2021Review
- The oncogenic role of protein kinase D3 in cancer.Journal of Cancer · 2021Review
- Rho GTPases: Big Players in Breast Cancer Initiation, Metastasis and Therapeutic Responses.Cells · 2020Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Protein kinase D3 (PKD3) is upregulated in triple-negative breast cancer (TNBC) and associated with cell proliferation and metastasis development but its precise pro-oncogenic function is unknown. Here we show that PKD3 is required for the maintenance of the TNBC stem cell population. The depletion of PKD3 in MDA-MB-231 cells reduced the cancer stem cell frequency in vitro and tumor initiation potential in vivo. We further provide evidence that the RhoGEF GEF-H1 is upstream of PKD3 activation in TNBC stem cells. Most importantly, pharmacological PKD inhibition in combination with paclitaxel synergistically decreased oncosphere and colony formation efficiency in vitro and tumor recurrence in vivo. Based on our results we propose that targeting the GEF-H1/PKD3 signaling pathway in combination with chemotherapy might provide an effective therapeutic option 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.