Genome-wide profiling of AP-1-regulated transcription provides insights into the invasiveness of triple-negative breast cancer.

QC 20150428
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.

Qiao, YichunDepartment of Biosciences and Nutrition, Novum, Karolinska Institute, Huddinge, Sweden (author)
Jonsson, PhilipUniversity of Houston, Texas, USA (author)
Wang, JianKarolinska Institute, Stockholm, Sweden (author)
Xu, LiDepartment of Biosciences and Nutrition, Novum, Karolinska Institute, Huddinge, Sweden (author)
Rouhi, PegahKarolinska Institute, Stockholm, Sweden (author)
Sinha, IndranilKarolinska Institutet (author)
Cao, YihaiKarolinska Institutet,Linköpings universitet,Avdelningen för kardiovaskulär medicin,Hälsouniversitetet,Karolinska Institute, Stockholm, Sweden; University of Leicester, Glenfield Hospital, Leicester, UK(Swepub:liu)yihca64 (author)
Williams, Cecilia,1969-University of Houston, TX, USA(Swepub:kth)u1ygqmuy (author)
Dahlman-Wright, KarinKarolinska Institutet (author)
Karolinska InstitutetDepartment of Biosciences and Nutrition, Novum, Karolinska Institute, Huddinge, Sweden (creator_code:org_t)

In:Cancer Research: American Association for Cancer Research74:14, s. 3983-39940008-54721538-7445

By the author/editor: Zhao, Chunyan; Qiao, Yichun; Jonsson, Philip; Wang, Jian; Xu, Li; Rouhi, Pegah; show more...; Sinha, Indranil; Cao, Yihai; Williams, Cecili ...; Dahlman-Wright, ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Cell and Molecul ...

By the university: Royal Institute of Technology; Linköping University; Karolinska Institutet

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