Abstract
Oral squamous cell carcinoma (OSCC) has a tendency to migrate and metastasize. WNT1-inducible signaling pathway protein 1 (WISP-1) is a cysteine-rich protein that belongs to the Cyr61, CTGF, Nov (CCN) family of matrix cellular proteins. The effect of WISP-1 on human OSCC cells, however, is unknown. Here, we showed that WISP-1 increased cell migration and intercellular adhesion molecule-1 (ICAM-1) expression in OSCC cells. Pretreatment of cells with integrin αvβ3 monoclonal antibody (mAb) significantly abolished WISP-1-induced cell migration and ICAM-1 expression. On the other hand, WISP-1-mediated cell motility and ICAM-1 upregulation were attenuated by ASK1, JNK, and p38 inhibitor. Furthermore, WISP-1 also enhanced activator protein 1 (AP-1) activation, and the integrin αvβ3 mAb, and ASK1, JNK, and p38 inhibitors reduced WISP-1-mediated AP-1 activation. Moreover, WISP-1 and ICAM-1 expression correlated with the tumor stage of patients with OSCC. Our results indicate that WISP-1 enhances the migration of OSCC cells by increasing ICAM-1 expression through the αvβ3 integrin receptor and the ASK1, JNK/p38, and AP-1 signal transduction pathways.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antibodies, Monoclonal / pharmacology
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CCN Intercellular Signaling Proteins / genetics
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CCN Intercellular Signaling Proteins / metabolism*
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Carcinoma, Squamous Cell / genetics
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Carcinoma, Squamous Cell / metabolism*
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Cell Line, Tumor
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Cell Movement / genetics
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Cell Movement / physiology*
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Humans
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Integrin alphaVbeta3 / antagonists & inhibitors
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Integrin alphaVbeta3 / metabolism
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Intercellular Adhesion Molecule-1 / genetics
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Intercellular Adhesion Molecule-1 / metabolism
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MAP Kinase Kinase Kinase 5 / genetics
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MAP Kinase Kinase Kinase 5 / metabolism*
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism*
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Signal Transduction
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Transcription Factor AP-1 / genetics
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Transcription Factor AP-1 / metabolism
Substances
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Antibodies, Monoclonal
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CCN Intercellular Signaling Proteins
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CCN4 protein, human
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Integrin alphaVbeta3
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Proto-Oncogene Proteins
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Transcription Factor AP-1
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Intercellular Adhesion Molecule-1
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MAP Kinase Kinase Kinase 5
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MAP3K5 protein, human
Grants and funding
This work was supported by grants from the National Science Council of Taiwan (NSC99-2320-B-039-003-MY3 and NSC100-2320-B-039-028-MY3); Taiwan Department of Health, China Medical University Hospital Cancer Research of Excellence (DOH102-TD-C-111-005). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.