ArticleOncotarget2016
A novel miR-34a target, protein kinase D1, stimulates cancer stemness and drug resistance through GSK3/β-catenin signaling in breast cancer.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- The mechanism of breast cancer stem cells and tumor microenvironment promoting radioresistance in breast cancer and its intervention strategies.Frontiers in immunology · 2026Pooled it
- Interplay between Epigenetic and Transcription Factors Mediating Drug Resistance via Stem Cells in Breast Cancer.ACS omega · 2025Review
- Modulatory effects of miRNAs in doxorubicin resistance: A mechanistic view.Functional & integrative genomics · 2024Review
- Article
- 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
- Protein Kinase D1 Signaling in Cancer Stem Cells with Epithelial-Mesenchymal Plasticity.Cells · 2022Article
- Extra Virgin Olive Oil (EVOO), a Mediterranean Diet Component, in the Management of Muscle Mass and Function Preservation.Nutrients · 2022Review
- The role of epigenetic modifications in drug resistance and treatment of breast cancer.Cellular & molecular biology letters · 2022Review
- Golgi Complex: A Signaling Hub in Cancer.Cells · 2022Review
- Tumour Stem Cells in Breast Cancer.International journal of molecular sciences · 2022Review
- The related miRNAs involved in doxorubicin resistance or sensitivity of various cancers: an update.Cancer chemotherapy and pharmacology · 2021Review
- The comprehensive landscape of miR-34a in cancer research.Cancer metastasis reviews · 2021Review
- Review
- Development of an arteriolar niche and self-renewal of breast cancer stem cells by lysophosphatidic acid/protein kinase D signaling.Communications biology · 2021Article
- The Role of GSK-3β in the Regulation of Protein Turnover, Myosin Phenotype, and Oxidative Capacity in Skeletal Muscle under Disuse Conditions.International journal of molecular sciences · 2021Review
- MicroRNAs as the critical regulators of Doxorubicin resistance in breast tumor cells.Cancer cell international · 2021Review
- Could miR-34a Inhibition be Used as a Tool to Overcome Drug Resistance in MCF-7 Cells Treated with Synthesized Steroidal Heterocycles?Asian Pacific journal of cancer prevention : APJCP · 2021Article
- MicroRNA-34a: Potent Tumor Suppressor, Cancer Stem Cell Inhibitor, and Potential Anticancer Therapeutic.Frontiers in cell and developmental biology · 2021Review
- RNA-binding proteins RBM-HuR, RBM3 and PODXL expression in urothelial carcinoma of the urinary bladder. Prognostic and clinical implications.Contemporary oncology (Poznan, Poland) · 2021Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
One of the properties of human breast cancer cells is cancer stemness, which is characterized by self-renewal capability and drug resistance. Protein kinase D1 (PRKD1) functions as a key regulator of many cellular processes and is downregulated in invasive breast cancer cells. In this study, we found that PRKD1 was upregulated in MCF-7-ADR human breast cancer cells characterized by drug resistance. Additionally, we discovered that PRKD1 expression was negatively regulated by miR-34a binding to the PRKD1 3'-UTR. PRKD1 expression increased following performance of a tumorsphere formation assay in MCF-7-ADR cells. We also found that reduction of PRKD1 by ectopic miR-34a expression or PRKD1 siRNA treatment resulted in suppressed self-renewal ability in breast cancer stem cells. Furthermore, we confirmed that the PRKD1 inhibitor CRT0066101 reduced phosphorylated PKD/PKCμ, leading to suppression of breast cancer stemness through GSK3/β-catenin signaling. PRKD1 inhibition also influenced apoptosis initiation in MCF-7-ADR cells. Tumors from nude mice treated with miR-34a or CRT0066101 showed suppressed tumor growth, proliferation, and induced apoptosis. These results provide evidence that regulation of PRKD1, a novel miR-34a target, contributes to overcoming cancer stemness and drug resistance in human breast cancer.
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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.