作者
Mateus Mota, Brandon J Metge, Dominique C Hinshaw, Heba A Alsheikh, Dongquan Chen, Rajeev S Samant, Lalita A Shevde
发表日期
2021/1
期刊
Molecular Oncology
简介
The expression of Merlin tumor suppressor protein encoded by Neurofibromin 2 (NF2) gene is remarkably decreased in metastatic breast cancer tissues. In order to recapitulate clinical evidence, we generated a unique, conditional Nf2‐knockout (Nf2−/−) mouse mammary tumor model. Merlin‐deficient breast tumor cells and Nf2−/− mouse embryonic fibroblasts (MEFs) displayed a robustly invasive phenotype. Moreover, Nf2−/− MEFs presented with notable alterations in redox management networks, implicating a role for Merlin in redox homeostasis. This programmatic alteration resonated with pathways that emerged from breast tumor cells engineered for Merlin deficiency. Further investigations revealed that NF2‐silenced cells supported reduced activity of the Nuclear factor, erythroid 2 like 2 antioxidant transcription factor, concomitant with elevated expression of NADPH oxidase enzymes. Importantly, mammary …
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M Mota, BJ Metge, DC Hinshaw, HA Alsheikh, D Chen… - Molecular Oncology, 2021