Low expression of PDK1 inhibits renal cell carcinoma cell proliferation, migration, invasion and epithelial mesenchymal transition through inhibition of the PI3K-PDK1-Akt pathway
Authors: Chao Hao
Qiu-Ming He
Ji Huang
Wei-Min Zhou
Xin-Hua Tu
Jin-Gao Li
Xiao-Dan Chen
Gong-Xian Wang
Gao-Liang Wu
Journal: Cellular Signalling (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Epithelial mesenchymal transition; Invasion; Migration; PDK1; PI3K-PDK1-Akt pathway
Affiliations: Jiangxi Medical College, Nanchang University, Nanchang 330006, PR China; Department of Urology, Jiangxi Cancer Hospital, Nanchang 330029, PR China., Department of Urology, Jiangxi Cancer Hospital, Nanchang 330029, PR China., Department of Radiotherapy, Jiangxi Cancer Hospital, Nanchang 330029, PR China., Department of Science and Education, Jiangxi Cancer Hospital, Nanchang 330029, PR China., Jiangxi Medical College, Nanchang University, Nanchang 330006, PR China; Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, PR China. Electronic address: ., Department of Urology, Jiangxi Cancer Hospital, Nanchang 330029, PR China. Electronic address: .

Abstract:  As the most commonly occurring form of primary renal tumor, renal cell carcinoma (RCC) is a malignancy accompanied by a high mortality rate. 3-phosphoinositide-dependent protein kinase 1 (PDK1) has been established as a protein target and generated considerable interest in both the pharmaceutical and academia industry. The aim of the current study was to investigate the effect of si-PDK1 on the RCC cell apoptosis, proliferation, migration, invasion and epithelial mesenchymal transition (EMT) in connection with the PI3K-PDK1-Akt pathway. Microarray analysis from the GEO database was adopted to identify differentially expressed genes (DEGs) related to RCC, after which the positive expression of the PDK1 protein in tissue was determined accordingly. The optimal silencing si-RNA was subsequently selected and RCC cell lines 786-O and A498 were selected and transfected with either a si-PDK1 or activator of the PI3K-PDK1-Akt pathway for grouping purposes. The mRNA and protein expressions of PDK1, the PI3K-PDK1-Akt pathway-, EMT- and apoptosis-related genes were then evaluated. The effect of si-PDK1 on cell proliferation, apoptosis, invasion and migration was then analyzed. Through microarray analysis of GSE6344, GSE53757, GSE14762 and GSE781, PDK1 was examined. PDK1 was determined to be highly expressed in RCC tissues. Si-PDK1 exhibited marked reductions in relation to the mRNA and protein expression of PDK1, PI3K, AKT as well as Vimentin while elevated mRNA and protein expressions of E-cadherin were detected, which ultimately suggested that cell migration, proliferation and invasion had been inhibited coupled with enhanced levels of cell apoptosis. While a notable observation was made highlighting that the PI3K-PDK1-Akt pathway antagonized the effect of PDK1 silencing. Taken together, the key observations of this study provide evidence suggesting that high expressions of PDK1 are found in RCC, while highlighting that silencing PDK1 could inhibit RCC cell proliferation, migration, invasion and EMT by repressing the PI3K-PDK1-Akt pathway. 

Retracted: No

PubPeer comments:
 Figs 5D,H. ![file] I am intrigued by the absence of background on these WBs, and the way the bands remain perfectly linear and retain the shape of the protein blobs as they move up the gel. Is it possible for the authors to upload the original scans of the gels? Numerous other papers have Figures which display the same qualities, hence my curiosity. I compiled a montage: ![] , 
 Fig 10A.  Si-PDK1 inhibits cell invasion of RCC cells. A, the invasive A498 cells in each group . ![file] Orange box for comparison with Fig 8A of [Mao et al (2018)] . ![file] , 
 #2 *[below]* Fig 10A again.  Si-PDK1 inhibits cell invasion of RCC cells. A, the invasive A498 cells in each group . *[above]* Fig 6a from [Fan et al (2020)] .  Cells in the basolateral chamber were observed under an inverted microscope . ![file] ,