Crumbs3 is expressed in oral squamous cell carcinomas and promotes cell migration and proliferation by affecting RhoA activity.
Crumbs3 is expressed in oral squamous cell carcinomas and promotes cell migration and proliferation by affecting RhoA activity.
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DOI：
10.3892/ol.2022.13293
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发表时间：
2022-06
期刊：
影响因子：
2.9
通讯作者：
中科院分区：
文献类型：
--
作者：
尽管近年来治疗取得了进展，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，开发新的分子靶向治疗方法是一个迫切需要解决的问题。本研究旨在探讨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分析显示，Crb3在OSCC患者和OSCC细胞系的组织中表达。敲低Crb3可降低OSCC细胞株的运动性，但不影响细胞增殖。然而，crb3敲除（KO）克隆表现出细胞迁移和增殖的减少。与亲本细胞相比，Crb3-KO克隆中上皮-间质转化标记的表达没有改变。异种移植小鼠肺转移模型显示，Crb3-KO克隆的转移潜力降低。正如Crb3-KO克隆所见，用RhoA激活抑制剂治疗后，OSCC细胞的运动性降低。通过使用亲和基质比较gtp结合的RhoA的数量来评估OSCC细胞中RhoA的血清诱导激活，发现Crb3-KO克隆中RhoA的激活降低。据我们所知，本研究首次证明了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。
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 Crb3 without affecting proliferation. However, Crb3-knockout (KO) clones exhibited decreases in both cell migration and proliferation. The expression of epithelial-mesenchymal transition markers was not altered in Crb3-KO clones compared with parent cells. A xenograft mouse model of lung metastasis revealed that the metastatic potential of Crb3-KO clones was reduced. As seen with Crb3-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 Crb3-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.
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影响因子：
11.2
作者：
Simpson, KJ;Dugan, AS;Mercurio, AM
通讯作者：
Mercurio, AM
DOI：
10.1002/hed.21529
发表时间：
2011-05-01
影响因子：
2.9
作者：
Kuperman, David I.;Auethavekiat, Vorachart;Morgensztern, Daniel
通讯作者：
Morgensztern, Daniel
影响因子：
4.8
作者：
Ellerbroek, SM;Wennerberg, K;Burridge, K
通讯作者：
Burridge, K
影响因子：
2
作者：
Pisani, Paolo;Airoldi, Mario;Zigliani, Angelo
通讯作者：
Zigliani, Angelo
影响因子：
64.5
作者：
TEPASS, U;THERES, C;KNUST, E
通讯作者：
KNUST, E