UMMS Affiliation
Department of Cell and Developmental Biology; Graduate School of Biomedical Sciences
Publication Date
2017-03-14
Document Type
Article
Disciplines
Cancer Biology | Cell Biology | Neoplasms | Oncology
Abstract
Runx1 is a well characterized transcription factor essential for hematopoietic differentiation and Runx1 mutations are the cause of leukemias. Runx1 is highly expressed in normal epithelium of most glands and recently has been associated with solid tumors. Notably, the function of Runx1 in the mammary gland and how it is involved in initiation and progression of breast cancer is still unclear. Here we demonstrate the consequences of Runx1 loss in normal mammary epithelial and breast cancer cells. We first observed that Runx1 is decreased in tumorigenic and metastatic breast cancer cells. We also observed loss of Runx1 expression upon induction of epithelial-mesenchymal transition (EMT) in MCF10A (normal-like) cells. Furthermore depletion of Runx1 in MCF10A cells resulted in striking changes in cell shape, leading to mesenchymal cell morphology. The epithelial phenotype could be restored in breast cancer cells by re-expressing Runx1. Analyses of breast tumors and patient data revealed that low Runx1 expression is associated with poor prognosis and decreased survival. We addressed mechanisms for the function of Runx1 in maintaining the epithelial phenotype and find Runx1 directly regulates E-cadherin; and serves as a downstream transcription factor mediating TGFbeta signaling. We also observed through global gene expression profiling of growth factor depleted cells that induction of EMT and loss of Runx1 is associated with activation of TGFbeta and WNT pathways. Thus these findings have identified a novel function for Runx1 in sustaining normal epithelial morphology and preventing EMT and suggest Runx1 levels could be a prognostic indicator of tumor progression.
Keywords
Runx1, breast cancer, epithelial Integrity, epithelial to mesenchymal transition, patient survival
Rights and Permissions
Copyright © 2017 Hong et al.
DOI of Published Version
10.18632/oncotarget.15381
Source
Oncotarget. 2017 Mar 14;8(11):17610-17627. doi: 10.18632/oncotarget.15381. Link to article on publisher's site
Journal/Book/Conference Title
Oncotarget
Related Resources
PubMed ID
28407681
Repository Citation
Hong, Deli; Messier, Terri L.; Tye, Coralee E.; Dobson, Jason; Fritz, Andrew J.; Sikora, Kenneth R.; Browne, Gillian; Stein, Janet L.; Lian, Jane B.; and Stein, Gary S., "Runx1 stabilizes the mammary epithelial cell phenotype and prevents epithelial to mesenchymal transition" (2017). Open Access Articles. 3117.
https://escholarship.umassmed.edu/oapubs/3117
Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.
Comments
Deli Hong is a student in the Graduate School of Biomedical Sciences at UMass Medical School.