Targeting Zfp148 activates p53 and reduces tumor initiation in the gut
Metrics: PDF 908 views | HTML 1649 views | ?
Anna Nilton1,*, Volkan I. Sayin1,2,*, Zhiyuan V. Zou1, Sama I. Sayin1, Cecilia Bondjers1, Nadia Gul1, Pia Agren1, Per Fogelstrand1, Ola Nilsson3, Martin O. Bergo4 and Per Lindahl1,2
1 Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, Gothenburg, Sweden
2 Department of Biochemistry, Institute of Biomedicine, Gothenburg, Sweden
3 Sahlgrenska Cancer Center, Institute of Biomedicine, Department of Pathology and Genetics, Gothenburg, Sweden
4 Sahlgrenska Cancer Center, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
* These authors have contributed equally to this work
Per Lindahl, email:
Keywords: intestinal tumors, tumor suppressor p53, apoptosis
Received: May 25, 2016 Accepted: July 13, 2016 Published: July 28, 2016
The transcription factor Zinc finger protein 148 (Zfp148, ZBP-89, BFCOL, BERF1, htβ) interacts physically with the tumor suppressor p53, but the significance of this interaction is not known. We recently showed that knockout of Zfp148 in mice leads to ectopic activation of p53 in some tissues and cultured fibroblasts, suggesting that Zfp148 represses p53 activity. Here we hypothesize that targeting Zfp148 would unleash p53 activity and protect against cancer development, and test this idea in the APCMin/+ mouse model of intestinal adenomas. Loss of one copy of Zfp148 markedly reduced tumor numbers and tumor-associated intestinal bleedings, and improved survival. Furthermore, after activation of β-catenin-the initiating event in colorectal cancer-Zfp148 deficiency activated p53 and induced apoptosis in intestinal explants of APCMin/+ mice. The anti-tumor effect of targeting Zfp148 depended on p53, as Zfp148 deficiency did not affect tumor numbers in APCMin/+ mice lacking one or both copies of Trp53. The results suggest that Zfp148 controls the fate of newly transformed intestinal tumor cells by repressing p53 and that targeting Zfp148 might be useful in the treatment of colorectal cancer.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.