ArticleBMC cancer2017
Protein kinase C α enhances migration of breast cancer cells through FOXC2-mediated repression of p120-catenin.
Article in BMC cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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40 citing papers in PubMed, 56 citations in OpenAlex.
- SERHL regulates invasion and metastasis through KLF16-PLCB1/PRKCA signaling in gastric cancer cells.Genes & diseases · 2026Article
- Aloe-Emodin Targeting FOXC2 Disrupts NETs Formation and EMT-Driven Postoperative Peritoneal Adhesion Through TGF-β1-Smad2/3 Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Functional analysis of the effect of isoimperatorin on human acute monocytic leukemia at the transcriptome level.Oncology letters · 2025Article
- Modulation of the Epithelial-mesenchymal transition process by Forkhead Box C2 in the repair of airway epithelium after injury.Respiratory research · 2025Article
- Effects of the carcinogen TCDD on δ-catenin stability and tumorigenic potential in prostate cancer cells.American journal of cancer research · 2025Article
- Biased signaling by mutant EGFR underlies dependence on PKCα in lung adenocarcinoma.Cell reports · 2024Article
- PKCActa pharmaceutica Sinica. B · 2024Article
- Convergent evolution of allele-specific gene expression that leads to non-small cell lung cancer in different human populations.Journal of applied genetics · 2024Article
- Identifying Key Genes Involved in Axillary Lymph Node Metastasis in Breast Cancer Using Advanced RNA-Seq Analysis: A Methodological Approach with GLMQL and MAS.International journal of molecular sciences · 2024Article
- System biology mediated assessment of molecular mechanism for sinapic acid against breast cancer: via network pharmacology and molecular dynamic simulation.Scientific reports · 2023Article
- Revisiting Estrogen for the Treatment of Endocrine-Resistant Breast Cancer: Novel Therapeutic Approaches.Cancers · 2023Review
- Article
- Molecular mechanisms of microRNA-216a during tumor progression.Cancer cell international · 2023Review
- Aberrant phosphorylation inactivates Numb in breast cancer causing expansion of the stem cell pool.The Journal of cell biology · 2022Article
- Protein Kinase C (PKC) Isozymes as Diagnostic and Prognostic Biomarkers and Therapeutic Targets for Cancer.Cancers · 2022Review
- ACE2 maybe serve as a prognostic biomarker in breast invasive carcinoma.Journal of clinical laboratory analysis · 2022Article
- 5-methylcytosine RNA methyltransferases and their potential roles in cancer.Journal of translational medicine · 2022Review
- Overarching roles of diacylglycerol signaling in cancer development and antitumor immunity.Science signaling · 2022Review
- Article
- PKC-mediated phosphorylation and activation of the MEK/ERK pathway as a mechanism of acquired trastuzumab resistance in HER2-positive breast cancer.Frontiers in endocrinology · 2022Article
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Authors and funding
5 authors at 3 institutions in 2 countries.
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Abstract
backgroundDespite recent advances in the diagnosis and treatment of breast cancer, metastasis remains the main cause of death. Since migration of tumor cells is considered a prerequisite for tumor cell invasion and metastasis, a pressing goal in tumor biology has been to elucidate factors regulating their migratory activity. Protein kinase C alpha (PKCα) is a serine-threonine protein kinase implicated in cancer metastasis and associated with poor prognosis in breast cancer patients. In this study, we set out to define the signaling axis mediated by PKCα to promote breast cancer cell migration.
methodsOncomine™ overexpression analysis was used to probe for PRKCA (PKCα) and FOXC2 expression in mRNA datasets. The heat map of PRKCA, FOXC2, and CTNND1 were obtained from the UC Santa Cruz platform. Survival data were obtained by PROGgene and available at http://www.compbio.iupui.edu/proggene . Markers for EMT and adherens junction were assessed by Western blotting and quantitative polymerase chain reaction. Effects of PKCα and FOXC2 on migration and invasion were assessed in vitro by transwell migration and invasion assays respectively. Cellular localization of E-cadherin and p120-catenin was determined by immunofluorescent staining. Promoter activity of p120-catenin was determined by dual luciferase assay using a previously validated p120-catenin reporter construct. Interaction between FOXC2 and p120-catenin promoter was verified by chromatin immunoprecipitation assay.
resultsWe determined that PKCα expression is necessary to maintain the migratory and invasive phenotype of both endocrine resistant and triple negative breast cancer cell lines. FOXC2 acts as a transcriptional repressor downstream of PKCα, and represses p120-catenin expression. Consequently, loss of p120-catenin leads to destabilization of E-cadherin at the adherens junction. Inhibition of either PKCα or FOXC2 is sufficient to rescue p120-catenin expression and trigger relocalization of p120-catenin and E-cadherin to the cell membrane, resulting in reduced tumor cell migration and invasion.
conclusionsTaken together, these results suggest that breast cancer metastasis may partially be controlled through PKCα/FOXC2-dependent repression of p120-catenin and highlight the potential for PKCα signal transduction networks to be targeted for the treatment of endocrine resistant and triple negative breast cancer.
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