Mitochondrial dysfunction promotes breast cancer cell migration and invasion through HIF1α accumulation via increased production of reactive oxygen species
Authors: Changjie Chen
Fazlul H Sarkar
Qingling Yang
Lucio Miele
Jia Ma
Zhiwei Wang
Qing Zhang
Jun Xia
Sulian Chen
Binbin Fang
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: Mitochondrial dysfunction; Cancer development; Reactive oxygen species; Cell migration; Cell invasion
Affiliations: Department of Biochemistry and Molecular Biology, Bengbu Medical College, Bengbu, Anhui, China.

Abstract:  Although mitochondrial dysfunction has been observed in various types of human cancer cells, the molecular mechanism underlying mitochondrial dysfunction mediated tumorigenesis remains largely elusive. To further explore the function of mitochondria and their involvement in the pathogenic mechanisms of cancer development, mitochondrial dysfunction clones of breast cancer cells were generated by rotenone treatment, a specific inhibitor of mitochondrial electron transport complex I. These clones were verified by mitochondrial respiratory defect measurement. Moreover, those clones exhibited increased reactive oxygen species (ROS), and showed higher migration and invasive behaviors compared with their parental cells. Furthermore, antioxidant N-acetyl cysteine, PEG-catalase, and mito-TEMPO effectively inhibited cell migration and invasion in these clones. Notably, ROS regulated malignant cellular behavior was in part mediated through upregulation of hypoxia-inducible factor-1 α and vascular endothelial growth factor. Our results suggest that mitochondrial dysfunction promotes cancer cell motility partly through HIF1α accumulation mediated via increased production of reactive oxygen species. 

Retracted: No

PubPeer comments:
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 2018 retraction. https: journals.plos.org plosone article?id=10.1371 journal.pone.0205288 In this article [1], concerns were raised about similarities between the following figure panels: Fig 2A, A clone + NAC cells and Fig 6D, A clone Fig 3A, A clone at 0 h and Fig 3A, B clone + NAC at 24 h Fig 2B, 4T1 cells and Fig 2B, C clone + NAC Fig 4C and 4D, H2O2 panels Fig 4D, control and Fig 6C, A clone Fig 4C, Mito-TEMPO and Fig 6D, A clone shRNA Fig 6C, A clone shRNA and Fig S2A, B clone Fig 5B, u03b2-actin lanes 1, 2 (labelled u201c4T1 cellsu201d and u201cC cloneu201d, respectively) and Fig 6B u03b2-actin lanes 1, 2 (labelled u201cA cloneu201d and u201cA clone shRNAu201d, respectively) Fig 5B u03b2-actin lane 5 (labelled u201cD clone + NACu201d) and Fig 6B HIF-1u03b1 lane 1 (labelled u201cA cloneu201d) In addition, it was noted that in Fig 3B, the 24 h panels each have clusters of cells that appear highly similar to and in the same location as cell clusters in the 0 h panels, with additional cells present in the 24 h panel. There are also cell clusters similar in appearance and location in the 0 h, 24 h, and 48 h data for the C clone, and in the 24 h and 48 h data for C clone + NAC. Vertical discontinuities suggestive of image splicing were also noted in Fig 5B between lanes 1 and 2 in the Hypoxic HIF-1u03b1 blot. A Correction was published in 2014 in which the authors provided new panels for Fig 3A (B clone + NAC, 24 h), and for the Western blot and cell images in Fig 6B, C, D [2]. Wayne State University investigated this work and found evidence of data duplications, image adjustments, and data mislabeling in Figs 2, 4, 5, and 6. The corresponding author did not provide the original data and records to the investigating committee. In light of these concerns, and in line with the institutionu2019s recommendation, the PLOS ONE Editors retract this article. QY and CC agreed with the retraction. JM, QZ, SC, BF, LM, FHZ, JX and ZW did not respond. , 
 https: retractionwatch.com 2018 10 04 cancer-researcher-who-once-tried-to-sue-critics-is-up-to-40-retracted-papers , 
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  Cancer researcher hit with 10-year ban on federal US funding for nearly 100 faked images https: retractionwatch.com 2020 08 07 cancer-researcher-hit-with-10-year-ban-on-federal-us-funding-for-nearly-100-faked-images Also, I was Peer 1 on post #2. The second image in my post #2, Figure 3, is not showing up correctly, so here it is again: * Figure 3A: The  A clone 0h panel looks similar to the  B clone+NAC 24h panel, as already brought up in comment #1. * Figure 3B: Several groups of cells appear to be visible multiple times across different panels. Boxes of the same color highlight groups that look similar. ![file] Reported to the journal in August 2014. ,