HIF-1α promotes ZEB1 expression and EMT in a human bladder cancer lung metastasis animal model
Authors: Kaijie Wu
Jianning Zhu
Mengzhao Zhang
Jin Zeng
Jinhai Fan
Peng Guo
Weiyi Wang
Xinyang Wang
Zhixin Huang
Jer-Tsong Hsieh
Hua Liang
Journal: Oncology Letters (2018)
Discipline: CLINICAL MEDICINE
Keywords: bladder cancer; epithelial-to-mesenchymal transition; metastasis.
Affiliations: Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China., Department of Urology, The Central Hospital of Wuhan, Wuhan, Hubei 430014, P.R. China., Department of Urology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, P.R. China., Department of Pathology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China., Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Abstract:  Lung is one of the most common sites for bladder cancer to metastasize. Although the involvement of the epithelial-to-mesenchymal transition (EMT) in bladder cancer progression has been established, the mechanism of EMT induction remains unclear. In order to investigate this, T24-parental (P) and T24-lung (L) bladder cancer cells were obtained from primary tumors and lung metastatic sites of an animal model with orthotopic spontaneous metastatic bladder cancer, according to a protocol previously described. Compared with T24-P cells, mesenchymal-like T24-L cells exhibited an increased ability in tumor invasion and metastasis, as well as an increased expression of hypoxia-inducible factor (HIF)-1α, zinc finger E-box-binding homeobox 1 (ZEB1), vimentin and N-cadherin and lower level of cytokeratin 18 were observed. Mechanistically, it was identified that HIF-1α increases ZEB1 expression and subsequently regulates the expression of EMT-related genes in both HIF-1α knocking down by siRNA and gain-in HIF-1α by hypoxia culture cell models. In addition, the expression of HIF-1α and ZEB1 in bladder cancer tissues were increased compared with normal bladder epithelial tissues, as well as significantly increased in the high-grade, invasive and metastatic bladder cancer tissues compared with low-grade, superficial and non-metastatic bladder cancer tissues by using immune-histochemical staining assay. Notably, the protein level of HIF-1α was positively associated with that of ZEB1 in bladder cancer tissues. Results from the present study indicate that HIF-1α promotes ZEB1 expression and EMT in the T24-L human bladder cancer lung metastasis animal model, suggesting that HIF-1α serves an important function in the metastasis of bladder cancer, and HIF-1α and ZEB1 may be potential targets for inhibiting bladder metastasis in the future. 

Retracted: No

PubPeer comments:
 Figure 2C and 2D appear to have images that overlap. *** ![file] , 
 We have known and attached great importance to your query about the above research published in oncology letters in 2018. After receiving your query, I have made it our top priority, and immediately took measures to investigate the relevant problems, and carefully re examined our manuscripts, original data and laboratory records. According to the survey results, we will actively revise, correct and feed back to the journals and your website. , 
 Corrected [10 June 2021] . ------------------------------------ Subsequently to the publication of the above article, an interested reader drew to the authorsu2019 attention that Fig. 2C and 2D apparently contained overlapping panels, suggesting that these data for purportedly different experiments had been derived from the same original source. The authors reu2011examined their original data, and realized that the errors arose inadvertently during the process of compiling the figure. Essentially, multiple photographs of random fields in two directions per sample had been captured, and one photograph of the T24u2011P group in a different direction was accidentally misu2011used for the T24u2011L siHIFu20111u03b1 group in Fig. 2C; another photograph of the T24u2011P group in a different direction was accidentally misu2011used for the T24u2011L group in Fig. 2D. A corrected version of Fig. 2 is shown below, featuring the corrected data panels for Fig. 2C and D. Note that the errors in the Figure did not affect either the results or the conclusions reported in this study. The authors are grateful to the Editor of Oncology Letters for granting them the opportunity to publish this corrigendum, and regret any inconvenience caused to the readership of the Journal. ,