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Copyright Nature Publishing Group Apr 2017

Abstract

Tumor cells often produce high levels of reactive oxygen species (ROS) and display an increased ROS scavenging system. However, the molecular mechanism that balances antioxidative and oxidative stress in cancer cells is unclear. Here, we determined that oncogenic multiple copies in T-cell malignancy 1 (MCT-1) activity promotes the generation of intracellular ROS and mitochondrial superoxide. Overexpression of MCT-1 suppresses p53 accumulation but elevates the manganese-dependent superoxide dismutase (MnSOD) level via the YY1-EGFR signaling cascade, which protects cells against oxidative damage. Conversely, restricting ROS generation and/or targeting YY1 in lung cancer cells effectively inhibits the EGFR-MnSOD signaling pathway and cell invasiveness induced by MCT-1. Signicantly, MCT-1 overexpression in lung cancer cells promotes tumor progression, necrosis and angiogenesis, and increases the number of tumor-promoting M2 macrophages and cancer-associated broblasts in the microenvironment. Clinical evidence further conrms that high expression of MCT-1 is associated with an increase in YY1, EGFR and MnSOD expression, accompanied by tumor recurrence, poor overall survival and EGFR mutation status in patients with lung cancers. Together, these data indicate that the MCT-1 oncogenic pathway is implicated in oxidative metabolism and lung carcinogenesis.

Details

Title
Oncogenic MCT-1 activation promotes YY1-EGFR-MnSOD signaling and tumor progression
Author
Tseng, H-y; Chen, Y-a; Jen, J; Shen, P-c; Chen, L-m; Lin, T-d; Wang, Y-c; Hsu, H-l
Pages
n/a
Publication year
2017
Publication date
Apr 2017
Publisher
Nature Publishing Group
e-ISSN
21579024
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
1891482300
Copyright
Copyright Nature Publishing Group Apr 2017