CEP55 promotes epithelial–mesenchymal transition in renal cell carcinoma through PI3K/AKT/mTOR pathway

Abstract

Purpose To study the detailed mechanisms of tumorigenesis and clinical outcomes of centrosomal protein 55 (CEP55) overexpression in renal cell carcinoma. Materials and methods Microarray analysis was performed to explore differentially expressed genes in five pairs of RCC tissues. Data of CEP55 expression and corresponding clinical information for 532 RCC patients of TCGA database were downloaded from cBioPortal. The expression of CEP55 in RCC tissues and cells was determined by real-time quantitative reverse transcription PCR (qRT-PCR), Western blot analysis and immunohistochemistry (IHC). Cells were transfected with siRNAs or lentivirus to regulate the expression of CEP55. The effects of CEP55 on proliferation, migration, invasion and epithelial-to-mesenchymal transition (EMT) of RCC cells were determined by MTS, migration and invasion assay and Western blot analysis. Results CEP55, one of the most upregulated genes in microarray analysis, was overexpressed in RCC tissues and cells. CEP55 expression was significantly correlated with poor outcome including neoplasm disease stage, histologic grade and TNM status, as well as survival status of patients. In vitro experiments showed that downregulation of CEP55 could dramatically inhibit RCC cell proliferation, migration and invasion, while overexpression of CEP55 could promote these biological behaviors. We further demonstrated that CEP55 knockdown suppressed epithelial-mesenchymal transition (EMT), which was mediated via upregulation of E-cadherin and downregulation of N-cadherin and ZEB1, through PI3K/AKT/mTOR pathway. In contrast, overexpression of CEP55 could promote EMT in RCC cells via the activation of PI3K/AKT/mTOR pathway. Importantly, inhibition of PI3K/AKT/mTOR pathway reduced the effects of CEP55 on the migration, invasion and EMT of RCC cells. Conclusion Our study showed that CEP55 could promote EMT through PI3K/AKT/mTOR pathway and might be an effective prognostic marker in RCC.

Acylglycerol kinase promotes tumour growth and metastasis via activating the PI3K/AKT/GSK3β signalling pathway in renal cell carcinoma

“…Several lines of evidence suggest that EMT promotes tumour metastasis in various cancers, including RCC [32][33][34][35][36][37]. Previous molecular analysis indicated that the high expression of AGK can induce the expression of HIF1a and promote EMT in cervical squamous carcinoma cells [11].…”

Neddylation blockade induces HIF-1α driven cancer cell migration via upregulation of ZEB1

“…Anti-HIF-1α previously made were used as described 41 . MLN4924 was synthesized, as described 11 . LY294002 (L9908) (a PI3K inhibitor), Rapamycin (mTOR inhibitor) and MK-2206 (s1078) (an AKT inhibitor), (Selleck Chemicals, Houston, TX, USA) were purchased from the indicated companies.…”

Identification of a Novel Signature and Construction of a Nomogram Predicting Overall Survival in Clear Cell Renal Cell Carcinoma

“…It is revealed that protein from these may also play a key role in ccRCC. The study of Chen et al (2019c) had shown that up-regulated CEP55 could promote epithelial-to-mesenchymal transition, migration, and invasion through the PI3K/AKT/mTOR pathway in RCC. Similarly, CEP55 was found to be up-regulated in multiple types of cancer and was related to unfavorable prognosis of non-small-cell lung cancer patients ( Jiang et al, 2018 ) and breast cancer patients ( Yin et al, 2018 ).…”