| Autor: |
Elizabeth A. Tovar, Menusha Arumugam, Curt J. Essenburg, Patrick S. Dischinger, Jamie L. Grit, Megan E. Callaghan, Rachael T.C. Sheridan, Lisa Turner, Corinne R. Esquibel, Kristin Feenstra, Zachary B. Madaj, Ian Beddows, Carrie R. Graveel, Matthew R. Steensma |
| Rok vydání: |
2022 |
| DOI: |
10.1101/2022.12.22.520633 |
| Popis: |
SUMMARYThe tumor suppressorNF1is a critical driver of sporadic breast cancer and NF-related breast cancers. We utilized distinctNf1-deficient immunocompetent rat models to investigateNf1function in mammary development and homeostasis. Here we demonstrate thatNf1deficiency dramatically accelerates mammary morphogenesis, alters TEB cell organization, and proliferation. Notably, we observed a shift in luminal-basal epithelial lineage commitment withinNf1-deficient lines with early tumor onset. In addition, we detected subpopulations of hybrid EMT cells (Ecad+/CK14+) within the invasive edge and stroma ofNf1-deficient tumors.Nf1deficiency restricted luminal progenitor potential and resulted in gene expression changes associated with decreased cell adhesion and increased EMT signatures. Together our findings support a model in whichNf1loss of function results in lineage plasticity throughout mammary morphogenesis and promotes EMT-mediated invasion. This study reveals a previously unknown role for the tumor suppressor neurofibromin in mammary homeostasis and phenotypic plasticity during breast cancer progression. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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