CIP2A interacts with AKT1 to promote the malignant biological behaviors of oral squamous cell carcinoma by upregulating the GSK‑3β/β‑catenin pathway

Che,Yilei; Zhang,Hui; Li,Hui; Wu,Xiaozhen

doi:10.3892/etm.2023.12213

CIP2A interacts with AKT1 to promote the malignant biological behaviors of oral squamous cell carcinoma by upregulating the GSK‑3β/β‑catenin pathway

Authors:
- Yilei Che
- Hui Zhang
- Hui Li
- Xiaozhen Wu
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Affiliations: Department of Stomatology, Aerospace Center Hospital, Beijing 100049, P.R. China
Published online on: September 20, 2023 https://doi.org/10.3892/etm.2023.12213
Article Number: 514
Copyright: © Che et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Oral squamous cell carcinoma (OSCC) is one of the most common malignancies worldwide, which is associated with a poor prognosis. The present study aimed to investigate the role of cancerous inhibitor of protein phosphatase 2A (CIP2A) in OSCC and its regulatory effect on AKT1. Firstly, CIP2A and AKT1 expression in OSCC cells was detected by western blotting. After silencing CIP2A, cell viability and cell proliferation were assessed using the Cell Counting Kit‑8 assay and 5‑ethynyl‑2'‑deoxyuridine staining. Cell apoptosis was evaluated by TUNEL staining and the expression of apoptosis‑related proteins was assessed using western blotting. Wound healing, Transwell and tube formation assays were performed to evaluate CAL‑27 cell migration, invasion and human umbilical vein endothelial cell (HUVEC) tube formation. The interaction between CIP2A and AKT1 was identified by co‑immunoprecipitation (co‑IP). In addition, AKT1 was overexpressed in CIP2A‑silenced CAL‑27 cells to perform rescue experiments to analyze the malignant biological functions of CAL‑27 cells. Finally, the expression of proteins in the glycogen synthase kinase (GSK)‑3β/β‑catenin pathway was determined by western blot analysis. Markedly elevated CIP2A and AKT1 expression was observed in OSCC cells. CIP2A knockdown inhibited the viability, proliferation, migration and invasion, and promoted the apoptosis of CAL‑27 cells. Concurrently, CIP2A loss‑of‑function attenuated tube formation. Results of Co‑IP confirmed there was an interaction between CIP2A and AKT1. Rescue experiments suggested that AKT1 overexpression alleviated the inhibitory effects of CIP2A knockdown on the viability, proliferation, migration and invasion of CAL‑27 cells, as well as tube formation in HUVECs . Additionally, CIP2A silencing significantly downregulated phosphorylated‑GSK‑3β and β‑catenin expression, which was reversed by AKT1 overexpression. In conclusion, CIP2A could interact with AKT1 to promote the malignant biological behaviors of OSCC cells by upregulating the GSK‑3β/β‑catenin pathway. These findings may provide a targeted therapy for OSCC treatment.

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