Sumoylation Pathway Is Required to Maintain the Basal Breast Cancer Subtype
Copyright policy )Sumoylation Pathway Is Required to Maintain the Basal Breast Cancer Subtype
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.
- Washington University in St. Louis United States
- University of Mary United States
- UNIVERSITY OF IOWA
- University of Iowa United States
Transcriptional Activation, Cancer Research, Mice, Nude, Breast Neoplasms, Transfection, Mice, Cell Line, Tumor, Animals, Humans, Neoplasms, Basal Cell, Gene Expression Profiling, Sumoylation, Cell Biology, Xenograft Model Antitumor Assays, Gene Expression Regulation, Neoplastic, Treatment Outcome, Oncology, Transcription Factor AP-2, Multigene Family, MCF-7 Cells, Small Ubiquitin-Related Modifier Proteins, Female
Transcriptional Activation, Cancer Research, Mice, Nude, Breast Neoplasms, Transfection, Mice, Cell Line, Tumor, Animals, Humans, Neoplasms, Basal Cell, Gene Expression Profiling, Sumoylation, Cell Biology, Xenograft Model Antitumor Assays, Gene Expression Regulation, Neoplastic, Treatment Outcome, Oncology, Transcription Factor AP-2, Multigene Family, MCF-7 Cells, Small Ubiquitin-Related Modifier Proteins, Female
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).79 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!