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Title: RUNX1 and RUNX3 protect against YAP-mediated EMT, stemness and shorter survival outcomes in breast cancer
Authors: Kulkarni, M 
Tan, T.Z 
Sulaiman, N.B.s
Lamar, J.M
Bansal, P
Cui, J 
Qiao, Y 
Ito, Y 
Keywords: protein kinase Yes
transcription factor RUNX1
transcription factor RUNX3
unclassified drug
Yes associated protein
animal experiment
animal model
breast cancer
breast epithelium cell
cancer growth
cancer prognosis
cancer recurrence
cell migration
cell proliferation
controlled study
epithelial mesenchymal transition
human tissue
major clinical study
protein expression
protein function
protein protein interaction
Issue Date: 2018
Citation: Kulkarni, M, Tan, T.Z, Sulaiman, N.B.s, Lamar, J.M, Bansal, P, Cui, J, Qiao, Y, Ito, Y (2018). RUNX1 and RUNX3 protect against YAP-mediated EMT, stemness and shorter survival outcomes in breast cancer. Oncotarget 9 (18) : 14175-14192. ScholarBank@NUS Repository.
Abstract: Hippo pathway target, YAP has emerged as an important player in solid tumor progression. Here, we identify RUNX1 and RUNX3 as novel negative regulators of oncogenic function of YAP in the context of breast cancer. RUNX proteins are one of the first transcription factors identified to interact with YAP. RUNX1 or RUNX3 expression abrogates YAP-mediated pro-tumorigenic properties of mammary epithelial cell lines in an interaction dependent manner. RUNX1 and RUNX3 inhibit YAP-mediated migration and stem-ness properties of mammary epithelial cell lines by co-regulating YAP-mediated gene expression. Analysis of whole genome expression profiles of breast cancer samples revealed significant co-relation between YAP- RUNX1/RUNX3 expression levels and survival outcomes of breast cancer patients. High RUNX1/RUNX3 expression proved protective towards YAP-dependent patient survival outcomes. High YAP in breast cancer patients' expression profiles co-related with EMT and stem-ness gene signature enrichment. High RUNX1/RUNX3 expression along with high YAP reflected lower enrichment of EMT and stem-ness signatures. This antagonistic activity of RUNX1 and RUNX3 towards oncogenic function of YAP identified in mammary epithelial cells as well as in breast cancer expression profiles gives a novel mechanistic insight into oncogene-tumor suppressor interplay in the context of breast cancer progression. The novel interplay between YAP, RUNX1 and RUNX3 and its significance in breast cancer progression can serve as a prognostic tool to predict cancer recurrence. © Kulkarni et al.
Source Title: Oncotarget
ISSN: 19492553
DOI: 10.18632/oncotarget.24419
Appears in Collections:Staff Publications

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