Abstract
CDK5 regulatory subunit associated protein 3 (CDK5RAP3) is a novel activator of PAK4 and processes important pro-metastatic function in hepatocarcinogenesis. However, it remains unclear if there are other mechanisms by which CDK5RAP3 promotes HCC metastasis. Here, we showed that in CDK5RAP3 stable knockdown SMMC-7721 HCC cells, p14(ARF) tumor suppressor was upregulated at protein and mRNA levels, and ectopic expression of CDK5RAP3 was found to repress the transcription of p14(ARF). Using chromatin immunoprecipitation assay, we demonstrated that CDK5RAP3 bound to p14(ARF) promoter in vivo. Furthermore, knockdown of p14(ARF) in CDK5RAP3 stable knockdown HCC cells reversed the suppression of HCC cell invasiveness mediated by knockdown of CDK5RAP3. Taken together, our findings provide the new evidence that overexpression of CDK5RAP3 promotes HCC metastasis via downregulation of p14(ARF).
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Carcinoma, Hepatocellular / metabolism*
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Carcinoma, Hepatocellular / pathology
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Cell Cycle Proteins
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Cell Line, Tumor
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Chromatin Immunoprecipitation
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Gene Knockdown Techniques
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Humans
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Intracellular Signaling Peptides and Proteins / physiology*
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Liver Neoplasms / metabolism*
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Liver Neoplasms / pathology
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Microscopy, Confocal
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Nerve Tissue Proteins / physiology*
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Promoter Regions, Genetic
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Reverse Transcriptase Polymerase Chain Reaction
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Tumor Suppressor Protein p14ARF / genetics
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Tumor Suppressor Protein p14ARF / physiology*
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Tumor Suppressor Proteins
Substances
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CDK5RAP3 protein, human
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Cell Cycle Proteins
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Intracellular Signaling Peptides and Proteins
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Nerve Tissue Proteins
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Tumor Suppressor Protein p14ARF
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Tumor Suppressor Proteins
Grants and funding
Our research is financially supported by The Hong Kong Research Grant Council (N_HKU715/08 and 7/CRF/09) (webpage:
http://www.ugc.edu.hk/eng/rgc/about/about.htm). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.