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The stem cell transcription factor ZFP57 induces IGF2 expression to promote anchorage-independent growth in cancer cells

Abstract

Several common biological properties between cancer cells and embryonic stem (ES) cells suggest the possibility that some genes expressed in ES cells might have important roles in cancer cell growth. The transcription factor ZFP57 is expressed in self-renewing ES cells and its expression level decreases during ES cell differentiation. This study showed that ZFP57 is involved in the anchorage-independent growth of human fibrosarcoma HT1080 cells in soft agar. ZFP57 overexpression enhanced, whereas knockdown suppressed, HT1080 tumor formation in nude mice. Furthermore, ZFP57 regulates the expression of insulin-like growth factor 2 (IGF2), which has a critical role in ZFP57-induced anchorage-independent growth. ZFP57 also promotes anchorage-independent growth in ES cells and immortal fibroblasts. Finally, immunohistochemical analysis revealed that ZFP57 is overexpressed in human cancer clinical specimens. Taken together, these results suggest that the ES-specific transcription factor ZFP57 is a novel oncogene.

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Acknowledgements

We are grateful to Drs Chuanhai Sun and Hitoshi Niwa for providing pCAGPMN(PvuII-MfeI)-CreER and pBRPyCAG-fKlf4-DsRed-IP, respectively. We also thank the Center for Biomedical Research and Education at Kanazawa University for the use of their DNA sequencer. This work was partly supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, a grant from the Hokkoku Foundation for Cancer Research and an Extramural Collaborative Research Grant from the Cancer Research Institute, Kanazawa University.

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Correspondence to H Koide.

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Tada, Y., Yamaguchi, Y., Kinjo, T. et al. The stem cell transcription factor ZFP57 induces IGF2 expression to promote anchorage-independent growth in cancer cells. Oncogene 34, 752–760 (2015). https://doi.org/10.1038/onc.2013.599

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