| First Author | Mota M | Year | 2021 |
| Journal | Mol Oncol | Volume | 15 |
| Issue | 4 | Pages | 942-956 |
| PubMed ID | 33410252 | Mgi Jnum | J:331301 |
| Mgi Id | MGI:7386981 | Doi | 10.1002/1878-0261.12896 |
| Citation | Mota M, et al. (2021) Merlin deficiency alters the redox management program in breast cancer. Mol Oncol 15(4):942-956 |
| abstractText | 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-specific Nf2(-/-) in an Mouse mammary tumor virus Neu + murine breast cancer model demonstrated accelerated mammary carcinogenesis in vivo. Tumor-derived primary organoids and cell lines were characteristically invasive with evidence of a dysregulated cellular redox management system. As such, Merlin deficiency programmatically influences redox imbalance that orchestrates malignant attributes of mammary/breast cancer. |
