Deduction of CDC42EP3 suppress development and progression of osteosarcoma.

Autor: Xu P; Department of Sports Medicine, The First Hospital of Jilin University, Jilin University, 71 Xinmin Street, Chaoyang District, Changchun City, Jilin Province, China., Li X; Department of Sports Medicine, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, 600 Yishan Road, Xuhui District, 200233, Shanghai City, China., Tang C; Department of Orthopedics, Shanghai Eighth People's Hospital, 8 Caobao Road, Xuhui District, Shanghai City, China., Wang T; Department of Orthopedics, Shanghai East Hospital, Shanghai Tong Ji University, 150 Jimo Road, Pudong District, Shanghai City, China., Xu J; Department of Sports Medicine, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, 600 Yishan Road, Xuhui District, 200233, Shanghai City, China. Electronic address: xupeng@jlu.edu.cn.
Jazyk: angličtina
Zdroj: Experimental cell research [Exp Cell Res] 2022 Mar 01; Vol. 412 (1), pp. 113018. Date of Electronic Publication: 2022 Jan 05.
DOI: 10.1016/j.yexcr.2022.113018
Abstrakt: Background: Osteosarcoma is a disease with high mortality of malignant tumors in children and adolescents. CDC42 effector protein 3 (CDC42EP3) has been reported to be associated with human cancer cell progression. This study aimed to investigate the biological function and preliminary molecular mechanism of CDC42EP3 in osteosarcoma.
Methods: CDC42EP3 expression in osteosarcoma was analyzed by immunohistochemical (IHC) staining. Secondly, the biological effects of CDC42EP3 in osteosarcoma cells was determined by loss/gain-of-function assays in vitro and in vivo.
Results: CDC42EP3 expression was higher in osteosarcoma tissue than in noncancerous tissue. The expression of CDC42EP3 was positively correlated with age, pathological stage and grade of patients with osteosarcoma. Furthermore, downregulation of CDC42EP3 suppressed tumor progression by inhibiting proliferation, migration and inducing apoptosis in vivo. Importantly, knockdown of CDC42EP3 reduced the expression of interstitial markers (N-cadherin, Vimentin and Snail) and increased the expression of epithelial markers (E-cadherin). In addition, CDC42EP3 knockdown downregulated PI3K and reduced the phosphorylation levels of AKT and mTOR. The mice xenograft model further confirmed that CDC42EP3 knockdown inhibited osteosarcoma growth in vitro.
Conclusions: In summary, these findings highlighted the significance of CDC42EP3 in tumor progression, which implicated CDC42EP3 as a promising candidate molecular target for osteosarcoma therapy.
(Copyright © 2022. Published by Elsevier Inc.)
Databáze: MEDLINE
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