Uraguchi M, Morikawa M, Shirakawa M, Sanada K, Imai K
Department of Oral Surgery, Graduate School of Dentistry, The Nippon Dental University, Tokyo, Japan.
J Dent Res. 2004 Apr;83(4):327-32. doi: 10.1177/154405910408300411.
The WNT family activates an oncogenic signaling mediated through beta-catenin and is up-regulated in a variety of malignant neoplasms. The signaling translocates beta-catenin into the nucleus and stimulates carcinoma cells in the epithelial-mesenchymal transition (EMT). However, WNT expression and signaling in oral carcinomas have not been examined. The present study focused on unveiling the involvement of WNTs in oral carcinomas, and showed that carcinoma cells express 11 of 19 WNT family members by reverse-transcription/PCR. WNT-expressing carcinoma cells exhibited increased beta-catenin levels in the cytoplasmic pool and translocation to the nucleus. The activation state of signaling correlated with the expression of membrane-type 1 matrix metalloproteinase, which degrades territorial matrices in carcinoma invasion. Immunohistochemistry disclosed that WNT3 expression and nuclear localization of beta-catenin were predominant in carcinoma cells at the invasive front. These results suggest that enhanced WNT expression and signaling accelerate the progression of carcinomas via activating EMTs and local invasiveness.
WNT家族激活通过β-连环蛋白介导的致癌信号通路，且在多种恶性肿瘤中表达上调。该信号通路使β-连环蛋白转位至细胞核，并刺激癌细胞发生上皮-间质转化（EMT）。然而，尚未对口腔癌中的WNT表达及信号通路进行研究。本研究着重揭示WNT在口腔癌中的作用，结果显示，通过逆转录/聚合酶链反应（RT/PCR）检测发现，癌细胞表达19种WNT家族成员中的11种。表达WNT的癌细胞胞质池中β-连环蛋白水平升高，并转位至细胞核。信号通路的激活状态与膜型1基质金属蛋白酶的表达相关，该酶在肿瘤侵袭过程中可降解局部基质。免疫组织化学显示，在侵袭前沿的癌细胞中，WNT3表达及β-连环蛋白的核定位较为显著。这些结果表明，WNT表达及信号通路增强可通过激活EMT和局部侵袭性加速肿瘤进展。
