Conversion of epithelial-to-mesenchymal transition to mesenchymal-to-epithelial transition is mediated by oxygen concentration in pancreatic cancer cells
Authors: Shuo Chen
Wan Run Lin
Li Wang
Xi Chen
Wenbin Yang
Wei Li
Yiming Li
Jiancang Ma
Gang Cao
Tao Shan
Xijuan Cui
Ya&#x27;an Kang
Journal: Oncology Letters (2018)
Discipline: CLINICAL MEDICINE
Keywords: epithelial-to-mesenchymal transition; hypoxia; hypoxia-inducible factor-1Œ±; mesenchymal- to-epithelial transition; pancreatic cancer.
Affiliations: Department of General Surgery, The Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China., The Institute for Population and Development Studies, School of Public Policy and Administration, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, P.R. China., Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China., Department of General Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China., Department of Gastrointestinal Surgery, Central Hospital of Zibo, Zibo, Shandong 255000, P.R. China., Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Abstract:  Tumor metastasis is accompanied by a two-stage process of epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET). Currently, the exact mechanisms underlying EMT-MET conversion are unclear. In the present study, the mechanisms by which primary sites (hypoxic) and homing sites (normoxic or hyperoxic) participate in EMT-MET conversion were evaluated. Pancreatic cancer cells were grown under different oxygenation conditions. Cell morphology and epithelial (E)-cadherin and vimentin expression were examined. Transwell chambers were used to examine tumor invasiveness, and scratch assays were performed to examine cell migration. Reverse transcription-polymerase chain reaction and western blot analysis were used to quantitate the mRNA and protein expression of E-cadherin, vimentin, Snail and hypoxia-inducible factor (HIF)-1Œ±. BxPc-3 and Panc-1 cells grown under hypoxic conditions demonstrated increased partial EMT, reduced E-cadherin expression, and increased vimentin expression, compared with cells grown under normoxic or hyperoxic conditions. Cells grown under hypoxic conditions also indicated increased migration and invasiveness. HIF-1Œ± mRNA and protein expression was increased in cells grown under hypoxic conditions. These changes were reversed when a specific inhibitor of the HIF-1Œ± receptor was used to block HIF-1Œ± signaling. Differences in oxygen concentration at primary sites and homing sites are important in the EMT-MET process, and the underlying mechanism may involve HIF-1Œ±-Snail signaling. 

Retracted: Yes

PubPeer comments:
 Initially I noted a repeated feature in Figure 2B (magenta boxes).  However on inspection with increased brightness, it seems as if many of the features have sharp edges as if they were copied and pasted (some identified with yellow arrows).  , 
 Figure 6 may have similar issues. *** Increased brightness and contrast  *** This project was supported by the National Natural Science Foundation of China (grant no. 81402583), Natural Science Foundation of Shaanxi Province (grant no. 2014JQ4165), Xi an Jiaotong University Education Foundation (grant no. xjj2014077) and the Hospital Fund of the Second Affiliated Hospital of the Health Science Center, Xi an Jiaotong University [grant nos. RC(XM)201402 and YJ(QN)201521]. , 
 Retracted [4 February 2022] .  Subsequently to the publication of the above paper, an interested reader drew to the authorsu2019 attention that a number of apparent anomalies existed with certain of the data presented in one of figures. Specifically, there appeared to be a pair of cells within the cellular images shown in the data panel of Fig. 2B (portraying the vimentin hypoxia experiment) that were matching on p. 7147. Furthermore, adjusting the contrast settings of the figure revealed the possibility that certain of the cells were not intrinsic to the original photographs taken of the presented data. Following an internal enquiry, the Editor of *Oncology Letters* shares the same concerns regarding the authenticity of these images that were raised by the interested reader; therefore, in view of the potential anomalies that have been identified and owing to a lack of overall confidence in the presented data, the Editor has decided to retract the above paper from the publication. After having passed on this decision to the authors, they were in agreement that the paper should be retracted. The Editor apologizes to the readership of the Journal for any inconvenience caused. , 
 **Announcement on the handling results of misconduct cases investigated and dealt with in 2022 (third batch)** via https: www.nsfc.gov.cn publish portal0 tab434 info87591.htm Regarding the forgery and falsification of research data in the papers published by Shan Tao Notification of processing results The National Natural Science Foundation of China Supervision Committee reviewed the paper  Shuo Chen # , Xi Chen # , Wei Li, Tao Shan*, Wan Run Lin, Jiancang Ma, Xijuan Cui, Wenbin Yang, Gang Cao, Yiming  published by Shan Tao et al. of Xi an Jiaotong University Li, Li Wang and Yaan Kang. Conversion of epithelial-to-mesenchymal transition to mesenchymal-to-epithelial transition is mediated by oxygen concentration in pancreatic cancer cells. Oncology letters, 2018, 15(5): 7144-7152.u201d (noted Fund No. 81402583) was investigated for suspected academic misconduct. After investigation, the paper has the problem of forging and tampering with the research data, and the corresponding author Shan Tao is mainly responsible for the above problems. After deliberation at the 14th meeting of the Fifth Supervision Committee of the National Natural Science Foundation of China and the 10th executive meeting of the National Natural Science Foundation of China in 2022, it was decided to follow the fortieth  Measures for Investigation and Handling of Scientific Research Misconduct in National Natural Science Foundation of China Projects . Articles 7 and 40, the National Natural Science Foundation of China Project  Research on ROS Remodeling CAFs Metabolic Transformation and Allocating Pancreatic Cancer to Growth in a Non-vascular Dependent Way (Approval No. 81402583), withdraw the allocated funds and cancel Shan Tao National Natural Science Foundation of China project application and participation qualification for 3 years (July 19, 2022 to July 18, 2025), and Shan Tao will be criticized. ,