Format

Send to

Choose Destination
Cancer Cell. 2014 Jun 16;25(6):748-61. doi: 10.1016/j.ccr.2014.04.008. Epub 2014 May 15.

Sumoylation pathway is required to maintain the basal breast cancer subtype.

Author information

1
Department of Surgery, University of Iowa, Iowa City, IA 52242, USA.
2
Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IA 52242, USA.
3
Department of Surgery, University of Iowa, Iowa City, IA 52242, USA; The Genome Institute, Washington University in St. Louis, St. Louis, MO 63108, USA.
4
Department of Surgery, University of Iowa, Iowa City, IA 52242, USA; Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IA 52242, USA; Department of Biochemistry, University of Iowa, Iowa City, IA 52242, USA. Electronic address: ronald-weigel@uiowa.edu.

Abstract

The TFAP2C/AP-2γ transcription factor regulates luminal breast cancer genes, and loss of TFAP2C induces epithelial-mesenchymal transition. By contrast, the highly homologous family member, TFAP2A, lacks transcriptional activity at luminal gene promoters. A detailed structure-function analysis identified that sumoylation of TFAP2A blocks its ability to induce the expression of luminal genes. Disruption of the sumoylation pathway by knockdown of sumoylation enzymes, mutation of the SUMO-target lysine of TFAP2A, or treatment with sumoylation inhibitors induced a basal-to-luminal transition, which was dependent on TFAP2A. Sumoylation inhibitors cleared the CD44(+/hi)/CD24(-/low) cell population characterizing basal cancers and inhibited tumor outgrowth of basal cancer xenografts. These findings establish a critical role for sumoylation in regulating the transcriptional mechanisms that maintain the basal cancer phenotype.

PMID:
24835590
PMCID:
PMC4096794
DOI:
10.1016/j.ccr.2014.04.008
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center