The role of WISP-1 in cell motility in human oral squamous cell carcinoma cells

• Main Authors: An-Chen Chang, 張安辰
• Other Authors: Jing-Yuan Chuang
• Format: Others
• Language: zh-TW
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/89382933833801462520

碩士 === 中國醫藥大學 === 醫學檢驗生物技術學系碩士班 === 101 === 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 apoptosis signal-regulating kinase 1 (ASK1) inhibitor (Thioredoxin), c-Jun N-terminal protein kinase (JNK) inhibitor (SP600125), and p38 inhibitor (SB203580). The stimulation of cells with WISP-1 increased ASK1, JNK, and p38 phosphorylation. 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. Taken together, 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.