ArticleBreast cancer research : BCR2020
PRKCQ inhibition enhances chemosensitivity of triple-negative breast cancer by regulating Bim.
Article in Breast cancer research : BCR, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 29 citations in OpenAlex.
- Anti-inflammatory and protective effects of Aloe vera on intestinal function in zebrafish.Journal of molecular histology · 2026Article
- Protein kinase C theta: evolution, regulation, and function.The Biochemical journal · 2026Review
- PRKCQ-TRIM22 axis promotes proliferation and metastasis of oral squamous cell carcinoma via autophagosome‒lysosome pathway activation.Cancer cell international · 2026Article
- Article
- Four-dimensional data independent acquisition proteomics and metabolomics reveal mechanisms of hydrogen-rich water at Zusanli (ST36) point against triple-negative breast cancer in mice.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2025Article
- Protein Kinase C Family: Structures, Biological Functions, Diseases, and Pharmaceutical Interventions.MedComm · 2025Review
- Association of PRKCQ variants with breast cancer susceptibility and clinicopathological features.BMC cancer · 2025Article
- Decoding dengue's neurological assault: insights from single-cell CNS analysis in an immunocompromised mouse model.Journal of neuroinflammation · 2025Article
- A PROTAC degrader suppresses oncogenic functions of PTK6, inducing apoptosis of breast cancer cells.Cell chemical biology · 2025Article
- Comprehensive analysis of telomere and aging-related signature for predicting prognosis and immunotherapy response in lung adenocarcinoma.Journal of cardiothoracic surgery · 2025Article
- Anti-Tumor Effects of Sheep Umbilical Cord Mesenchymal Stem Cells on Melanoma Cells.International journal of molecular sciences · 2025Article
- The Landscape of Potential Targeted Treatments and Chemotherapy Efficacy Biomarkers for TNBC.Breast cancer (Dove Medical Press) · 2025Review
- Clustering single-cell RNA sequencing data via iterative smoothing and self-supervised discriminative embedding.Oncogene · 2024Article
- The Transformative Role of 3D Culture Models in Triple-Negative Breast Cancer Research.Cancers · 2024Review
- MiR-128-1-5p inhibits cell proliferation and induces cell apoptosis via targeting PRKCQ in colorectal cancer.Cancer biology & therapy · 2023Article
- Anoikis resistance--protagonists of breast cancer cells survive and metastasize after ECM detachment.Cell communication and signaling : CCS · 2023Review
- Screening of feature genes related to immune and inflammatory responses in periodontitis.BMC oral health · 2023Article
- Box C/D snoRNA SNORD89 influences the occurrence and development of endometrial cancer through 2'-O-methylation modification of Bim.Cell death discovery · 2022Article
- Article
- Targeting Protein Kinase C for Cancer Therapy.Cancers · 2022Review
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundProtein kinase C theta, (PRKCQ/PKCθ) is a serine/threonine kinase that is highly expressed in a subset of triple-negative breast cancers (TNBC) and promotes their growth, anoikis resistance, epithelial-mesenchymal transition (EMT), and invasion. Here, we show that PRKCQ regulates the sensitivity of TNBC cells to apoptosis triggered by standard-of-care chemotherapy by regulating levels of pro-apoptotic Bim.
methodsTo determine the effects of PRKCQ expression on chemotherapy-induced apoptosis, shRNA and cDNA vectors were used to modulate the PRKCQ expression in MCF-10A breast epithelial cells or triple-negative breast cancer cells (MDA-MB231Luc, HCC1806). A novel PRKCQ small-molecule inhibitor, 17k, was used to inhibit kinase activity. Viability and apoptosis of cells treated with PRKCQ cDNA/shRNA/inhibitor +/-chemotherapy were measured. Expression levels of Bcl2 family members were assessed.
resultsEnhanced expression of PRKCQ is sufficient to suppress apoptosis triggered by paclitaxel or doxorubicin treatment. Downregulation of PRKCQ also enhanced the apoptosis of chemotherapy-treated TNBC cells. Regulation of chemotherapy sensitivity by PRKCQ mechanistically occurs via regulation of levels of Bim, a pro-apoptotic Bcl2 family member; suppression of Bim prevents the enhanced apoptosis observed with combined PRKCQ downregulation and chemotherapy treatment. Regulation of Bim and chemotherapy sensitivity is significantly dependent on PRKCQ kinase activity; overexpression of a catalytically inactive PRKCQ does not suppress Bim or chemotherapy-associated apoptosis. Furthermore, PRKCQ kinase inhibitor treatment suppressed growth, increased anoikis and Bim expression, and enhanced apoptosis of chemotherapy-treated TNBC cells, phenocopying the effects of PRKCQ downregulation.
conclusionsThese studies support PRKCQ inhibition as an attractive therapeutic strategy and complement to chemotherapy to inhibit the growth and survival of TNBC cells.
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