The stem cell transcription factor ZFP57 induces IGF2 expression to promote anchorage-independent growth in cancer cells.
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.
Department of Stem Cell Biology, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, Japan.
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Tada
Department of Gastroenterologic Surgery, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, Japan.
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Yamaguchi
Department of Stem Cell Biology, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, Japan.
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Kinjo
Department of Stem Cell Biology, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, Japan.
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Song
Department of Stem Cell Biology, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, Japan.
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Akagi
Department of Gastroenterologic Surgery, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, Japan.
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Takamura
Department of Gastroenterologic Surgery, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, Japan.
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Ohta
Department of Stem Cell Biology, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, Japan.
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Yokota
Department of Stem Cell Biology, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, Japan.
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Koide
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D012097:Repressor Proteins; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
D004268:DNA-Binding Proteins; C035170:IGF2 protein, human; D012097:Repressor Proteins; D014157:Transcription Factors; C531063:ZFP57 protein, human; D007335:Insulin-Like Growth Factor II