American Association for Cancer Research
00085472can133396-sup-fig5.pdf (126.25 kB)

Supplementary Figure 5 from Genome-wide Profiling of AP-1–Regulated Transcription Provides Insights into the Invasiveness of Triple-Negative Breast Cancer

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journal contribution
posted on 2023-03-30, 22:03 authored by Chunyan Zhao, Yichun Qiao, Philip Jonsson, Jian Wang, Li Xu, Pegah Rouhi, Indranil Sinha, Yihai Cao, Cecilia Williams, Karin Dahlman-Wright

PDF file - 128KB, Validation of AP-1 mediated downregulation of E-cadherin expression through transcriptional induction of ZEB2 in the Hs578T TNBC cell line.



Triple-negative breast cancer (TNBC) is an aggressive clinical subtype accounting for up to 20% of all breast cancers, but its malignant determinants remain largely undefined. Here, we show that in TNBC the overexpression of Fra-1, a component of the transcription factor AP-1, offers prognostic potential. Fra-1 depletion or its heterodimeric partner c-Jun inhibits the proliferative and invasive phenotypes of TNBC cells in vitro. Similarly, RNAi-mediated attenuation of Fra-1 or c-Jun reduced cellular invasion in vivo in a zebrafish tumor xenograft model. Exploring the AP-1 cistrome and the AP-1–regulated transcriptome, we obtained insights into the transcriptional regulatory networks of AP-1 in TNBC cells. Among the direct targets identified for Fra-1/c-Jun involved in proliferation, adhesion, and cell–cell contact, we found that AP-1 repressed the expression of E-cadherin by transcriptional upregulation of ZEB2 to stimulate cell invasion. Overall, this work illuminates the pathways through which TNBC cells acquire invasive and proliferative properties. Cancer Res; 74(14); 3983–94. ©2014 AACR.

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