GP73 promotes invasion and metastasis of bladder cancer by regulating the epithelial-mesenchymal transition through the TGF-β1/Smad2 signalling pathway
Authors: Ge-Liang Liu
Bo Liu
Han-Jie Yang
Tian Liu
Journal: Journal of cellular and molecular medicine (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Golgi membrane protein 73; TGF-β1/Smad2 signalling pathway; bladder cancer; epithelial-mesenchymal transition; invasion
Affiliations: Department of Urology, Pingxiang Affiliated, Southern Medical University, Pingxiang, China., Department of General Surgery, Xiangya 2nd Hospital of Central South University, Changsha, China.

Abstract:  This study investigated the effects of Golgi membrane protein 73 (GP73) on the epithelial-mesenchymal transition (EMT) and on bladder cancer cell invasion and metastasis through the TGF-β1/Smad2 signalling pathway. Paired bladder cancer and adjacent tissue samples (102) and normal bladder tissue samples (106) were obtained. Bladder cancer cell lines (T24, 5637, RT4, 253J and J82) were selected and assigned to blank, negative control (NC), TGF-β, thrombospondin-1 (TSP-1), TGF-β1+ TSP-1, GP73-siRNA-1, GP73-siRNA-2, GP73-siRNA-1+ TSP-1, GP73-siRNA-1+ pcDNA-GP73, WT1-siRNA and WT1-siRNA + GP73-siRNA-1 groups. Expressions of GP73, TGF-β1, Smad2, p-Smad2, E-cadherin and vimentin were detected using RT-qPCR and Western blotting. Cell proliferation, migration and invasion were determined using MTT assay, scratch testing and Transwell assay, respectively. Compared with the blank and NC groups, levels of GP73, TGF-β1, Smad2, p-Smad2, N-cadherin and vimentin decreased, and levels of WT1 and E-cadherin increased in the GP73-siRNA-1 and GP73-siRNA-2 groups, while the opposite results were observed in the WT1 siRNA, TGF-β, TSP-1 and TGF-β + TSP-1 groups. Cell proliferation, migration and invasion notably decreased in the GP73-siRNA-1 and GP73-siRNA-2 groups in comparison with the blank and NC groups, while in the WT1 siRNA, TGF-β, TSP-1 and TGF-β + TSP-1 groups, cell migration, invasion and proliferation showed the reduction after the EMT. These results suggest that GP73 promotes bladder cancer invasion and metastasis by inducing the EMT through down-regulating WT1 levels and activating the TGF-β1/Smad2 signalling pathway. 

Retracted: No

PubPeer comments:
 Two images in Figure 1 appear to overlap, with horizontal flip and adjustments to scale. Green boxes roughly indicate area of concern. *** ![file] , 
 #1 Other readers on social media correctly noted that the green boxes should encompass a greater area of overlap, and noted a repeated image (in red). *** ![file] , 
 Some images in the right side of Figure 8A appear to overlap, after rotation etc. *** ![file] *** ![file] , 
 Fig 5G,  protein band pattern of 5637 cells . ![file] At left, Fig 4B from [Tian et al (2018)] .  Western blot analysis demonstrates that miRu2010485 reduces the protein expressions of RhoA, ILu20106, TGFu2010u03b2, and p38MAPKs as well as the extent of pu2010p38MAPK . At right, Fig 7C from [Han et al (2018)] .  Gray value of cAMP, PKA and CREB1 protein bands . Other manifestations are linked in those threads (also [Zhao et al, 2018)] . ![] Fig 5H,  protein band pattern of 253J cells ![file] Compare, e.g. Fig 5 from [Lin et al (2018)] , Fig 9A from [Wu et al (2018)] and 5c from [Wu et al (2018)] . More manifestations are linked in that thread. ![] , 
 #2 Fig 1 continues to surprise. ![file] A panel is shared with Fig 9 of  MicroRNA-433 inhibits oral squamous cell carcinoma cells by targeting FAK ([Wang et al 2017] ). ![file] , 
 #3 More overlaps in Fig 8A. ![file] Red box: see Fig 7A of  Effects of LncRNA-HOST2 on cell proliferation, migration, invasion and apoptosis of human hepatocellular carcinoma cell line SMMC-7721 ([Liu et al 2017] ) **[retracted]**. ![] and Fig 8(a) of  Effects of microRNA-135a on the epithelialu2013mesenchymal transition, migration and invasion of bladder cancer cells by targeting GSK3u03b2 through the Wnt u03b2-catenin signaling pathway ([Mao et al 2018] ). ![] Other boxes: Fig 5C of  Long nonu2010coding RNA H19 is responsible for the progression of lung adenocarcinoma by mediating methylationu2010dependent repression of CDH1 promoter ([Gao et al 2019] ). ![file] , 
 Fig 1 yet again: ![] Fig 9 of  MicroRNA-433 inhibits oral squamous cell carcinoma cells by targeting FAK ([Wang et al 2017] ): ![] - *[above]* Fig 1a from  Effects of microRNA-135a on the epithelialu2013mesenchymal transition, migration and invasion of bladder cancer cells by targeting GSK3u03b2 through the Wnt u03b2-catenin signaling pathway ([Mao et al 2018] ). - *[below]* Fig 1 from  Higher expression of FOXOs correlates to better prognosis of bladder cancer ([Zhang et al 2017] ). ![] ,