Journal
PLOS ONE
Volume 8, Issue 10, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0078022
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Funding
- National Science Council of Taiwan [NSC99-2320-B-039-003-MY3, NSC100-2320-B-039-028-MY3]
- Taiwan Department of Health, China Medical University Hospital Cancer Research of Excellence [DOH102-TD-C-111-005]
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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 avb3 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 avb3 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 avb3 integrin receptor and the ASK1, JNK/p38, and AP-1 signal transduction pathways.
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