ArticleBMC cancer2018
Analysis of oncogenic activities of protein kinase D1 in head and neck squamous cell carcinoma.
Article in BMC cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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Who cites it
9 citing papers in PubMed, 17 citations in OpenAlex.
- Potential Prognostic Role of Protein Kinase D Isoforms in Head and Neck Cancers.International journal of molecular sciences · 2024Article
- Protein kinase D1 overexpression potentiates epidermal growth factor signaling pathway in MCF-7 cells.Molecular biology reports · 2023Article
- Overarching roles of diacylglycerol signaling in cancer development and antitumor immunity.Science signaling · 2022Review
- Construction and Validation of a UPR-Associated Gene Prognostic Model for Head and Neck Squamous Cell Carcinoma.BioMed research international · 2022Article
- Article
- Multifaceted Functions of Protein Kinase D in Pathological Processes and Human Diseases.Biomolecules · 2021Review
- State-Transition Analysis of Time-Sequential Gene Expression Identifies Critical Points That Predict Development of Acute Myeloid Leukemia.Cancer research · 2020Article
- Protein Kinase D1 Is Increased in Tumor Tissue, Correlates With Advanced Tumor Features and Worse Prognosis of Non-Small Cell Lung Cancer.Technology in cancer research & treatmentArticle
- Protein Kinase D 1 Predicts Poor Treatment Response and Unfavorable Survival of Bortezomib-Based Treatment, and Its Knockdown Enhances Drug Sensitivity to Bortezomib in Multiple Myeloma.Technology in cancer research & treatmentArticle
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundHead and neck squamous cell carcinoma (HNSCC) is the sixth leading cause of cancer death in the US. The protein kinase D (PKD) family has emerged as a promising target for cancer therapy with PKD1 being most intensively studied; however, its role in HNSCC has not been investigated.
methodsThe expression of PKD was evaluated in human HNSCC by quantitative RT-PCR, Western blot and immunohistochemistry. Cell proliferation, wound healing, and matrigel invasion assays were performed upon siRNA-mediated knockdown of PKD1 in HNSCC cells, and subcutaneous xenograft mouse model was established by implantation of the stable doxycycline (Dox)-inducible PKD1 expression cell lines for analysis of tumorigenic activity in vivo.
resultsPKD1 was frequently downregulated in HNSCC cell lines at both transcript and protein levels. In human HNSCC tissues, PKD1 was significantly down-regulated in localized tumors and metastases, and in patient-paired tumor tissues as compared to their normal counterparts, which was in part due to epigenetic modification of the PRKD1 gene. The function of PKD1 in HNSCC was analyzed using stable doxycycline-inducible cell lines that express native or constitutive-active PKD1. Upon induction, the rate of proliferation, survival, migration and invasion of HNSCC cells did not differ significantly between the control and PKD1 overexpressing cells in the basal state, and depletion of endogenous PKD1 did not impact the proliferation of HNSCC cells. However, the median growth rate of the subcutaneous HNSCC tumor xenografts over time was elevated with PKD1 induction, and the final tumor weight was significantly increased in Dox-induced vs. the non-induced tumors. Moreover, induced expression of PKD1 promoted bombesin-induced cell proliferation of HNSCC and resulted in sustained ERK1/2 activation in response to gastrin-releasing peptide or bombesin stimulation, suggesting that PKD1 potentiates GRP/bombesin-induced mitogenic response through the activation of ERK1/2 in HSNCC cells.
conclusionsOur study has identified PKD1 as a frequently downregulated gene in HNSCC, and functionally, under certain cellular context, may play a role in GRP/bombesin-induced oncogenesis in HNSCC.
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