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.
Highlights
Oral squamous cell carcinoma (OSCC) represents 1–2% of all human malignancies
The mechanism of metastasis is a complicated and multistage process; our study showed that WNT1-inducible signaling pathway protein 1 (WISP-1) induces cell migration and the expression of intercellular adhesion molecule-1 (ICAM-1) in human OSCC cells
We provided the evidence that ICAM-1 acts as a crucial transducer of cell signaling, regulating cell migration, and WISP-1 acts as a critical mediator of the metastasis activity of OSCC cells in the tumor microenvironment
Summary
Oral squamous cell carcinoma (OSCC) represents 1–2% of all human malignancies. It is the most common head and neck cancer and is characterized by poor prognosis and low survival rate. CCN family proteins are mostly secreted and are associated to the extracellular matrix (ECM) which has been demonstrated to play important roles in tumor development, including tumor survival, proliferation, migration, and invasion [6,7]. They may connect signaling pathways and facilitate crosstalk between the epithelium and stroma [4]. These data suggest that WISP-1 plays a critical role during cancer development and metastasis
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