Yokoyama Yusuke, Iioka Hidekazu, Horii Arata, Kondo Eisaku
Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
Department of Otolaryngology, Head and Neck Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
Oncol Lett. 2022 Jun;23(6):173. doi: 10.3892/ol.2022.13293. Epub 2022 Apr 13.
Despite the recent progression of treatments, the 5-year survival rate of patients with oral squamous cell carcinoma (OSCC) is still poor. One of the most critical factors affecting prognosis is tumor metastasis. Developing novel molecular targeted therapies by analyzing the molecular pathway of OSCC metastasis is an urgent issue. The present study aimed to characterize the expression and function of crumbs3 (Crb3) in OSCC cell migration. Immunohistochemistry and immunoblotting revealed that Crb3 was expressed in tissues from patients with OSCC and OSCC cell lines. The motility of OSCC cell lines was decreased by knockdown of without affecting proliferation. However, knockout (KO) clones exhibited decreases in both cell migration and proliferation. The expression of epithelial-mesenchymal transition markers was not altered in -KO clones compared with parent cells. A xenograft mouse model of lung metastasis revealed that the metastatic potential of -KO clones was reduced. As seen with -KO clones, the motility of OSCC cells was decreased by treatment with inhibitors of RhoA activation. Serum-induced activation of RhoA in OSCC cells was evaluated by comparing the amount of GTP-bound RhoA using affinity matrices, revealing that RhoA activation was decreased in -KO clones. To the best of our knowledge, the present study was the first to demonstrate that Crb3 was expressed in squamous cell carcinoma tissues and promoted cell migration and proliferation, which was associated with RhoA activation in OSCC cells.
尽管近年来治疗方法有所进展，但口腔鳞状细胞癌（OSCC）患者的5年生存率仍然很低。影响预后的最关键因素之一是肿瘤转移。通过分析OSCC转移的分子途径来开发新的分子靶向治疗是一个紧迫的问题。本研究旨在表征crumbs3（Crb3）在OSCC细胞迁移中的表达和功能。免疫组织化学和免疫印迹显示，Crb3在OSCC患者组织和OSCC细胞系中表达。敲低Crb3可降低OSCC细胞系的运动性，而不影响其增殖。然而，敲除（KO）克隆的细胞迁移和增殖均降低。与亲本细胞相比，Crb3-KO克隆中上皮-间质转化标志物的表达没有改变。肺转移的异种移植小鼠模型显示，Crb3-KO克隆的转移潜能降低。与Crb3-KO克隆的情况一样，用RhoA激活抑制剂处理可降低OSCC细胞的运动性。通过使用亲和基质比较结合GTP的RhoA的量来评估血清诱导的OSCC细胞中RhoA的激活，结果显示Crb3-KO克隆中RhoA激活降低。据我们所知，本研究首次证明Crb3在鳞状细胞癌组织中表达，并促进细胞迁移和增殖，这与OSCC细胞中的RhoA激活有关。
