Wnt5b promotes the cell motility essential for metastasis of oral squamous cell carcinoma through active Cdc42 and RhoA

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  • TAKESHITA Akinori
    Department of Oral and Maxillofacial Surgery Ⅱ，Osaka University Graduate School of Dentistry
  • IWAI Soichi
    Department of Oral and Maxillofacial Surgery Ⅱ，Osaka University Graduate School of Dentistry
  • MORITA Yoshihiro
    Department of Oral and Maxillofacial Surgery Ⅱ，Osaka University Graduate School of Dentistry
  • NIKI Atsuko
    Department of Oral and Maxillofacial Surgery Ⅱ，Osaka University Graduate School of Dentistry
  • HAMADA Masakazu
    Department of Oral and Maxillofacial Surgery Ⅱ，Osaka University Graduate School of Dentistry
  • YURA Yoshiaki
    Department of Oral and Maxillofacial Surgery Ⅱ，Osaka University Graduate School of Dentistry

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Other Title
  • Wnt5bは活性型Cdc42およびRhoAを介して口腔扁平上皮癌の転移に重要な細胞運動能を亢進する
  • 二次出版 Wnt5bは活性型Cdc42およびRhoAを介して口腔扁平上皮癌の転移に重要な細胞運動能を亢進する
  • ニジ シュッパン Wnt5b ワ カッセイガタ Cdc42 オヨビ RhoA オ カイシテ コウコウ ヘンペイ ジョウヒ ガン ノ テンイ ニ ジュウヨウ ナ サイボウ ウンドウノウ オ コウシン スル

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Abstract

<p>The activation of Wnt signaling has been reported in many types of squamous cell carcinoma. In this study, we used human oral squamous cell carcinoma (OSCC) cells with different metastatic potentials to investigate the involvement of Wnt signaling in metastasis. In addition, we aimed to elucidate the characteristic biological features related to high metastatic potential and to identify new target molecules for the suppression of OSCC lymph node metastasis. We compared SAS-Venus (SAS OSCC cells expressing green fluorescent protein) and SAS-LM8, which is a highly metastatic cell line derived from SAS-Venus by in vivo selection. The SAS-LM8 cell line had greater ability of migration and invasion than did SAS-Venus. Furthermore, a higher number of filopodia-like protrusive structures were produced in SAS-LM8 cells than in SAS-Venus cells, and the levels of active Cdc42 and active RhoA protein were higher in SAS-LM8 cells than in SAS-Venus cells. We did not observe any differences in the expression of Wnt/beta-catenin target genes between the two cell lines ; however, the mRNA levels of Wnt5b were higher in SAS-LM8 cells than in SAS-Venus cells. To confirm the involvement of Wnt5b in migration in OSCC cells, we examined the effects of the siRNA-mediated knockdown of Wnt5b in SAS-Venus cells and SAS-LM8 cells. The siRNA treatment significantly inhibited migration and the formation of filopodia-like protrusive structures. Conversely, when stimulated with Wnt5b, the migration and formation of filopodia-like protrusions were significantly enhanced, and the levels of active Cdc42 and active RhoA proteins also increased. These results indicate that Wnt5b is involved in the migration ability of OSCC cells through active Cdc42 and RhoA.</p>

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