Crumbs3 is expressed in oral squamous cell carcinomas and promotes cell migration and proliferation by affecting RhoA activity

Yokoyama,Yusuke; Yokoyama,Yusuke; Iioka,Hidekazu; Iioka,Hidekazu; Horii,Arata; Horii,Arata; Kondo,Eisaku; Kondo,Eisaku

doi:10.3892/ol.2022.13293

Crumbs3 is expressed in oral squamous cell carcinomas and promotes cell migration and proliferation by affecting RhoA activity

Authors:
- Yusuke Yokoyama
- Hidekazu Iioka
- Arata Horii
- Eisaku Kondo
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Affiliations: 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
Published online on: April 13, 2022 https://doi.org/10.3892/ol.2022.13293
Article Number: 173
Copyright: © Yokoyama et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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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